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THE    THERAPY    OF 
SYPHILIS 

ITS    DEVELOPMENT    AND 
PRESENT    POSITION 

BY 

DR.  PAUL  MULZER 

OF    BERLIN 

WITH    A    PREFACE    BY 

PROF.    P.    UHLENHUTH,    M.D. 

PRIVY    COUNCILLOR 
TRANSLATED    BY 

A.   NEWBOLD 


^^^ 


NEW    YORK 
REBMAN     COMPANY 

1123    BROADWAY 


Entered  at  Stationers'  Hall 

All  rights  reserved 


DEDICATED 

WITH    THE    GREATEST    RESPECT 
TO 

HIS  ROYAL  HIGHNESS 

LOUIS    FERDINAND,    M.D. 

PRINCE    OF    BAVARIA 


PREFACE 

It  is  not  to  exact  scientific  research  that 
we  owe  a  number  of  the  best  and  most 
effectual  of  our  drugs  used  in  combating 
infectious  diseases,  but  instead  to  rough 
empiricism.  I  may  mention  here  quinine, 
iodine,  saHc^dic  acid,  mercury^  and  arsenic. 
The  phrase  ''  practice  surpasses  theory  " 
has  even  now  a  certain  justification;  and, 
indeed,  in  the  present  era  of  exact  experi- 
mental therapy,  we  cannot  quite  dispense 
with  these  unscientific  -  sounding  words- 
The  difference  between  now  and  formerly 
only  consists  in  the  fact  that,  in  many 
infectious  diseases  against  which  we  wage 
war,  armed  with  these  drugs,  we  have 
become  acquainted  with  the  instigators 
of  the  disease  ;  further,  we  can  to  a  certain 
extent  transfer  these  to  animals,  and  conse- 


PREFACE 

quently  carry  out  our  experiments  upon 
them.  These  latter,  however,  are  now 
performed  quite  differently  to  what  they 
were  formerly,  for,  as  the  result  of  our 
exact  knowledge,  we  can  ocularly  ob- 
serve and  follow  under  the  microscope 
the  destructive  action  of  many  drugs  upon 
the  microparasites  in  question.  This  is 
an  enormous  advance,  and  is  highly  grati- 
fying to  both  physician  and  researcher, 
who  are  thus  able  to  realise  the  attractive 
and  fertile  stage  the  study  of  chemotherapy 
has  attained. 

From  the  empirical  a  causal  therapy  has 
been  evolved.  It  is  also  conceivable  that 
the  knowledge  of  the  expert  and  purposeful 
application  of  this  expedient  is  due  first 
of  all  to  bacteriological  science,  the  duty 
of  which  consists,  not  only  in  searching 
for  the  causes  of  infectious  diseases,  but 
also  in  destroying  the  exciters  both  in- 
side and  outside  the  human  and  animal 
body. 

This  applies  to-day  especially  to  aromatic 

vi 


PREFACE 

arsenic  preparations,  which  are  of  para- 
mount medical  interest ;  their  efficacy  has 
been  tested  in  bacteriological  laboratories, 
and  they  have  been  proved  to  be  powerful 
weapons  in  the  struggle  against  diseases 
due  to  trypanosomes  and  spirochaetes. 

In  relapsing  fever  and  syphilis — the  most 
dreaded  human  spirochaete  diseases — these 
arsenic  preparations  have  already  yielded 
many  gratif^dng  results.  Nevertheless,  we 
must  acknowledge  that  even  now  we  are 
far  from  possessing  an  ideal  specific  drug, 
as,  apparently,  with  nearly  all  the  arsenic 
preparations  which  have  been  employed 
so  far,  there  is  a  certain  neurotropic  action. 
At  the  same  time,  we  must  not  abandon 
aromatic  arsenic  preparations  in  the  treat- 
ment of  syphilis,  especially  as  they  are 
effective  in  those  cases  in  which  iodine  and 
mercury  fail. 

In  the  book  before  us,  by  Dr.  Mulzer, 
my  esteemed  colleague  in  the  domain  of 
experimental  s^^philis,  the  general  practi- 
tioner will  be  enlightened  as  to  the  present 

vii 


PREFACE 

position  of  modern  specific  therapy ;  he 
will  be  shown  what  was  formerly  accom- 
plished, and  at  the  same  time  its  develop- 
ment up  to  the  present  day  will  be  demon- 
strated to  him. 

As  the  work  of  the  Imperial  Health 
Bureau  paved  the  way  for  this  improve- 
ment and  practically  promoted  it  by 
the  discovery  of  the  Spirochceta  pallida, 
by  researches  in  experimental  syphilis  of 
rabbits,  and,  above  all,  by  the  construction 
and  development  of  the  experimental  basis 
of  the  organic  arseno-therapy  of  spirilloses, 
and  especially  of  syphilis,  it  is  a  particular 
pleasure  to  send  this  book  on  its  way  with 
a  foreword  and  to  associate  this  with  the 
wish  that  arseno-therapy  in  its  present 
form  and  future  evolution  may  bring  a 
blessing  to  suffering  humanity. 

PAUL  UHLENHUTH 

{Imperial  Health  Bureau)^ 

Berlin, 

Gross  Lichterfelde, 

December  i6,  1910. 

viii 


INTRODUCTION 

After  F.  Schaudinn  discovered  the  Spiro- 
chcBta  pallida  at  the  Imperial  Health  Bureau, 
in  1905,  and,  in  common  with  E.  Hoffmann, 
reported  on  the  constant  appearance  of 
this  peculiar  micro-organism  in  the  most 
varied  infectious  products  of  specific  dis- 
ease, the  pendulum  of  syphilitic  research 
swung  forward  unexpectedly  and  vigor- 
ously. The  epoch-making  communications 
of  Schaudinn  and  Hoffmann  were  further 
tested  by  many  researchers.  Within  a 
short  time  numerous  works  appeared  which 
confirmed  and  extended  these  results,  so 
that  the  probability  of  the  5.  pallida  being 
the  exciter  of  syphilis  became  greater  and 
greater.  It  was  soon  proved  that  specific 
disease  must  exist  in  the  organism  if  one 
could  testify  to  the  certain  presence  of  the 

ix 


INTRODUCTION 

S.  pallida.  If  found  in  an  ulcer  or  erosion, 
which  could  not  be  positively  diagnosed 
clinically,  this  might  be  pronounced  to  be 
a  primary  syphilitic  affection.  Later,  the 
appearance  of  secondary  phenomena  always 
confirmed  the  accuracy  of  this  diagnosis. 
Subsequently,  when  syphilis  was  experi- 
mentally produced  in  animals,  it  was  regu- 
larly possible  to  prove  the  presence  of  the 
S.  pallida,  and  to  therapeutically  influence 
this  form  of  disease  by  means  of  specific 
remedies.  All  these  facts  have  taught  us 
that  the  5.  pallida  is  really  the  exciter  of 
syphilis. 

These  results  were  first  practically  applied 
in  confirming  the  diagnosis  of  syphilis. 
To  Erich  Hoffmann  is  due  the  service  of 
having  again  and  again  referred  to  the 
extraordinary  diagnostic  importance  of  the 
presence  of  S.  pallida  in  doubtful  cases 
of  disease. 

A  further  advance  in  modern  syphilitic 
research  is  indicated  by  the  introduction 
of    serum    diagnosis   by   A.    Wassermann, 


INTRODUCTION 

A.  Neisser,  and  C.  Bruck.  Supported  by 
the  experience  and  observations  of  numerous 
teachers,  there  is  no  longer  any  doubt  that 
the  positive  result  of  the  Wassermann  test 
in  all  probability  indicates  that  the  in- 
dividual, whose  blood -serum  gives  this 
reaction,  must  at  some  time  have  suffered 
from  specific  infection.  A  preliminary  con- 
dition for  such  a  conclusion  is  naturally 
skill  in  carrying  out  the  reaction  and  an 
irreproachable  technique. 

Some  time  before  the  discovery  of  the 
5.  pallida  Metschnikoff  and  Roux  had 
succeeded  in  transmitting  syphilis  to  apes. 
Acting  on  this  discovery,  it  was  possible 
for  A.  Neisser  and  his  collaborators,  after 
working  for  years  in  Batavia,  to  experi- 
mentally solve  upon  apes  many  highly 
valuable  problems  of  the  pathology  and 
therapy  of  syphilis.  Bertarelli,  Levaditi, 
Parodi,  Hoffmann,  Lohe  and  the  author, 
Uhlenhuth,  and  Weidanz,  Grouven,  Trufh, 
and  other  researchers  also  succeeded  later 
in   experimentally   infecting   rabbits   with 

xi 


INTRODUCTION 

syphilis  ;  these  results,  however,  were  re- 
garded more  or  less  as  accidental  and 
exceptional.  Uhlenhuth  and  I,  after  sys- 
tematically arranged  experimental  studies 
on  syphilis  of  the  scrotum  in  rabbits  were 
the  first  to  demonstrate  that  these  animals, 
more  than  all  others,  including  the  lower 
apes,  are  specially  adapted  for  this  kind  of 
experimental  research.  It  is  on  this  fact, 
which  was  later  also  confirmed  by  other 
authors  — such  as  Truffi,  Menzincesku, 
Tomasczewski,  and  M.  Koch — that  the 
results  which  indicated  the  modern  chemo- 
therapy of  syphilis  were  finally  based. 


xu 


CONTENTS 


HAGE 


Preface  by  Privy  Councillor  Uhlenhuth        v 

Introduction  (Discovery  of  the  Spirochceia 
'pallida,  Wassermann  Reaction,  Experi- 
mental Syphilis)      -  -  -  -      ix 

Influence  of  the  Results  of  Syphilitic 
Research  upon  the  Former  Mercurial 
Therapy  of  Syphilis  -  -  -        i 

Chemotherapy  of  Syphilis  : 

I.  Atoxyl    -  -  -  -  -      12 

II.  Arsacetin  (Ehrlich)     -  -  -      27 

III.  Atoxylate  of  Mercury  (Uhlenhuth)      29 

IV.  Hectine  -  -  -  -  -      37 

V.    SOAMIX      -  -  -  -  -        3S 

VI.  Arsenophenylglycin    -  -  -      40 

VII.   DiOXYDIAMIDOARSENOBENZOL  (EhRLICH- 

Hata  "  606 ")          -  -            -      44 
I.  Chemical    Constitution,  Experi- 
ments ON  Animals     -  -           -45 
xiii 


CONTENTS 

PAGE 

VII.  DioxYDiAMiDOARSENOBENZOL — continued  : 

2.  Suspension  of  Solutions  which  are 

Ready  for  Use  -  -  -  50 

[a]  Alkaline  Solutions        -  -  51 

(&)  Neutral  Emulsions        -  -  58 

(c)  Kromayer's  Paraffin  Emulsion  65 

3.  Technique  OF  Injection        -  -  71 

[a)  Intramuscular  Injection  -  71 

(&)  Subcutaneous  Injection  -  73 

(c)  Intravenous  Injection  -  -  75 

4.  Direct    Local    Secondary    Effects 

OF  the  Injection  -  -      81 

5.  Effect  of  Arsenobenzol  upon   the 

Organism  in  General    -  -      86 

6.  Effect  of  Arsenobenzol  on   Syphi- 

litic Diseases  of  the  Primary, 
Secondary,  and  Tertiary 
Periods    -  -  -  -      89 

(a)  Primary  Affections        -  -      92 

(6)  Early     Stage     of     Secondary 

Syphilis    -  -  -  -      98 

(c)  The  Late  Stage  of  Secondary 

Syphilis  and  Tertiary  Syphilis     iio 

{d)  Malignant  Syphilis  and  Ulcer- 
ous Tertiary  Forms  respec- 
tively      -  - 


119 


XIV 


CONTENTS 

PAGE 

VII.  DioxYDiAMiDOARSENOBENZOL — continued  : 
(e)  Treatment   of    Syphilitic    Dis- 
eases OF  the  Eyes  with  Arseno- 

BENZOL        -  -  -  -      122 

(/)  Syphilis  of  the  Internal  Or- 
gans         -           -           -  .    126 

(g)  Meta-  and  Para-Syphilitic  Dis- 
eases, including  Tabes  and 
Paralysis             -           -  -    128 

(h)  Hereditary  Syphilis       -  -    133 

7.  Dosage            -           -           .  .    13^ 

8.  Influencing    the    Result    of  the 

Wassermann  Reaction  by  Means 
OF  Treatment  with  Arseno- 
benzol  -  -  -  -    141 

9.  Relapses         -  -  .  .    149 

10.  Secondary  Effects    -  -  -    172 

11.  Epicrisis  _  _  -  -     ig6 

Literature       -  -  -  -  -    205 

Index    -  -  -  -  -  -    225 

Authorities  referred  to       -  -  -    245 


XV 


THE 

THERAPY  OF  SYPHILIS 


INFLUENCE  OF  THE  RESULTS  OF 
SYPHILITIC  RESEARCH  UPON  THE 
FORMER  MERCURIAL  THERAPY 

A  The  experience  of  a  century  has  taught 
^  us  that,  of  all  the  drugs  used  in  the  treat- 
ment of  syphilis,  without  doubt  mercury 
is  the  most  powerful  and  effective.  In 
earlier  tim.es  many  errors  in  its  therapeutic 
application,  from  ignorance  of  cause  and 
effect,  often  resulted  in  the  serious  injury 
of  the  individual,  who  had  been  treated  too 
drastically.  If,  in  consequence,  this  drug 
is  to-day  still  discredited  in  many  lay  circles, 
we  know  that,  with  expert  medical  applica- 
tion and  control,  mercury  is  at  the  present 
time   the   sole   drug   capable    of    effecting 


THE  THERAPY  OF  SYPHILIS 

the  definite  cure  of  syphilis,  even  if  this 
is  not  so  in  all  cases.  The  accuracy  of 
this  statement  is  testified  to  by  the  fact 
"  that  severe  tertiary  symptoms  appear 
most  frequently  in  untreated  or  inade- 
quately treated  cases,  whereas,  on  the 
other  hand,  the  best  protection  against 
this  is  early,  energetic  mercurial  treat- 
ment "  (E.  Lesser). 

I  will  not  go  into  further  details  here, 
as  to  the  special  indications  for  this  therapy, 
and  respectively  as  to  the  different  mercurial 
preparations  and  their  application  in  the 
individual  stages  of  syphilis.  I  will  merely 
briefly  recapitulate  when  we  began  the 
general  treatment — i.e.,  until  the  discovery 
of  the  exciter  of  syphilis.  There  were  two 
opinions  with  regard  to  this.  In  the  one, 
the  specific  treatment  was  begun  as  soon 
as  possible — i.e.,  immediately  after  the 
recognition  of  the  primary  affection  ;  in  the 
other,  it  was  believed  that  it  was  necessary 
to  wait  until  the  appearance  of  the  first 
secondary  symptoms  indicated  a  generalisa- 


THE  THERAPY  OF  SYPHILIS 

tion  of  the  syphilitic  virus  ;  the  adherents 
to  this  view  included  some  of  our  most 
celebrated  syphilidologists.  In  this  thera- 
peutic procedure,  they  relied  upon  their 
experience  and  that  of  other  teachers, 
who  considered  the  action  of  mercury  was 
most  lasting  in  the  general  syphilitic  stage, 
and  that  it  had  never  been  possible  to 
succeed  in  arresting  the  disease  by  early 
treatment,  and  thus  prevent  an  outbreak 
of  general  infection.  Above  all,  however, 
it  was  believed  that  one  must  wait  until 
the  eruption  of  roseola  appeared,  because 
it  was  only  then  that  one  could  diagnose 
syphilis  with  absolute  certainty,  as  even 
the  most  experienced  teacher  might  be 
deceived  by  the  manifold  and  frequently 
uncharacteristic  forms  of  the  phenomena 
of  the  primary  affection. 

This  hesitation  disappears  now  that  we 
are  capable  of  obtaining  the  proof  of  the 
presence  of  the  Spirochceta  pallida  in 
doubtful  cases  of  diseased  tissue,  occasion- 
ally after  repeated  careful  examinations, 

3 


THE  THERAPY  OF  SYPHILIS 

and    of    recognising    these    absolutely    as 
primary  syphilitic  lesions. 

Further,  animal  experiment  has  also 
removed  the  objection  that  it  is  only  with 
the  outbreak  of  the  secondary  symptoms 
that  the  virus  is  spread  over  the  organism, 
and  is  then  more  accessible  to  general 
specific  treatment.  Hoffmann  was  able 
to  prove  experimentally  that  the  blood  of 
syphilitics  induced  syphilis  in  apes,  which 
had  been  inoculated  with  it,  about  the 
sixth  week  after  the  infection,  therefore 
several  weeks  before  the  outbreak  of  the 
secondary  symptoms.  Neisser  was  able  to 
demonstrate  that  the  internal  organs  of 
apes  already  contained  syphihtic  virus  at 
the  time  of  the  appearance  of  the  primary 
affection,  and,  indeed,  mostly  much  earlier, 
from  the  fact  that,  by  inoculating  the 
spleen-liver-bone-marrow  pulp  of  an  animal 
diseased  in  this  way  on  to  other  healthy 
animals,  typical  forms  of  syphilitic  disease 
could  be  induced.  In  the  same  way,  Uhlen- 
huth  and  I  were  able  to  confirm  this  fact 

4 


THE  THERAPY  OF  SYPHILIS 

by  the  primary  inoculation  syphilis  of 
rabbits.  Another  circumstance  which  must 
be  taken  into  consideration  as  testifying  to 
this  is  the  fact  that,  according  to  the  state- 
ment of  most  authors,  the  Wassermann 
reaction  shows  a  positive  result  in  nearly 
half  the  cases  in  the  primary  stage. 

From  the  clinical  observations  of  Hol- 
lander, Hoffmann,  Thalmann,  and  others, 
we  know,  however,  that  in  the  so-called 
''  early  treatment  "  of  syphilis  by  excision 
of  the  primary  affection,  with  subsequent 
drastic  doses  of  mercury,  even  if  perfect 
cure  is  extremely  rare,  it  is  possible  to 
diminish  the  intensity  of  the  further  course 
of  the  disease  to  some  extent. 

It  is,  therefore,  necessary  for  the  practi- 
tioner to  begin  general  treatment  as  soon 
as  ever  syphilis  has  been  diagnosed — i.e., 
directly  it  has  been  possible  to  prove  the 
presence  of  the  5.  pallidcB  in  the  suspected 
diseased  material.  By  extending  the  ex- 
cision into  the  healthy  part  as  far  as  possible, 
one  must  endeavour  to  remove  the  primary 

5 


THE  THERAPY  OF  SYPHILIS 

afection,  so  as  not  to  renounce  the  possi- 
bility of  arresting  the  syphiUs,  or  at  least 
of  preventing  a  further  immigration  of  the 
spirochaetes  into  the  organism  from  here. 
Where  this  is  not  possible,  in  consequence 
of  the  anatomical  position,  we  must  try  to 
destroy  them  by  cauterisation,  hot  air 
treatment,  or  by  covering  with  mercurial 
plaster,  and  finally  annihilate  the  spiro- 
chaetes everywhere,  by  injections  of  soluble 
mercurial  or  arsenical  preparations  (for 
example,  hydrargyrum  oxycyanatum, 
atoxyl,  Ehrlich-Hata).  ''  From  the  point 
of  view  of  prophylaxis  also,  it  is  very 
desirable  to  reduce  the  chancre  as  soon  as 
possible,  and  so  avoid  its  being  the  source 
of  fresh  infections  ''  (Hoffmann). 

From  my  experience,  I  find  we  do  not 
select  our  strongest  mercurial  preparations 
at  the  beginning  of  general  treatment,  so 
that  there  is  a  possibility  of  increasing 
the  dose  in  individual  cases.  But  instead, 
we  try  to  augment  the  intensity  of  the  pre- 
liminary treatment  by  its  longer  duration. 

6 


THE  THERAPY  OF  SYPHILIS 

The  animal  experiments  of  Neisser  and 
his  collaborators  have  demonstrated  that 
mercury   is   a   direct   remedy   for   specific 
disease,  and,  indeed,  not  only  of  manifest 
syphilis,    but    also    in    the    latent    stages. 
From  this  Neisser  infers  the  justice  of  our 
former  therapy — namely,   that   in  human 
syphilis  mercury  is  not  to  be  administered 
solely   as   a  systematic  remedy,   but  also 
in  those  cases  where  clinically  we  can  deter- 
mine no  symptoms,  but,  nevertheless,  know, 
partly  from  general  experience  and  partly 
from  the  serum  diagnosis,  that  there  is  still 
specific  poison  in  the  body.     Further,  if  we 
reflect  that  in  most  of  the  forms  of  disease 
spirochaetes  are  present  during  the  second 
period,   and  are  therefore  capable  of  re- 
maining for  a  very  long  time  in  the  body, 
all  these  facts  testify  fully  to  the   justice 
— indeed,  the  necessity — of  chronic  inter- 
mittent treatment  of  syphilis. 

With  regard  to  the  question  as  to  how 
far  the  result  of  the  Wassermann  reaction 
should  influence  our  therapeutic  treatment, 

7 


THE  THERAPY  OF  SYPHILIS 

this  has  not  been  explained  at  the  present 
time.  As  long  as  we  do  not  definitely 
know  the  genuine  nature  of  this  reaction, 
a  complete  solution  of  the  problem  cannot 
be  anticipated.  The  majority  of  authors 
agree  that  the  positive  result  of  the  Wasser- 
mann  reaction  indicates  with  absolute  cer- 
tainty that  active  syphilitic  virus  is  still 
present  in  the  organism.  It  naturally 
follows  that,  in  every  case  in  which  the 
serum  reaction  gives  a  positive  result,  anti- 
syphilitic  treatment  should  be  introduced, 
quite  immaterially  whether  manifest  symp- 
toms are  present  or  not.  Other  teachers, 
amongst  whom  I  include  myself,  acknow- 
ledge, it  is  true,  that  the  specific  therapy 
exercises  a  certain  influence  upon  the  result 
of  the  reaction,  but  they  believe  that  this 
has  too  little  constancy  and  proportion  to 
require  a  special  therapy  to  which  the 
organism  is  not  quite  indifferent,  especially 
in  the  more  advanced  cases  of  syphilis.  In 
my  opinion,  the  practical  value  of  the 
Wasserm.ann  reaction  lies  principally  in  the 

8 


THE  THERAPY  OF  SYPHILIS 

diagnostic  domain,  and  respectively  of 
differential  diagnosis.  Therapeutically  this 
reaction  can  be  taken  advantage  of,  in  that 
a  positive  result  of  the  same  proves,  with 
a  probability  bordering  on  certainty,  that 
specific  infection  has  occurred  in  the  in- 
dividual whose  blood  gives  this  reaction. 
We  must  then  make  an  exact  anamnesis 
of  the  course  of  the  disease  and  of  former 
treatment,  our  further  therapeutic  measures 
being  first  of  all  dependent  on  this  result. 
The  same  thing  applies,  certainly  in  a 
far  less  degree,  to  an  occasional  negative 
result  of  the  Wassermann  reaction.  In 
itself  this  naturally  proves  nothing.  It  is 
only  when  the  examination  of  the  blood, 
repeated  at  varying  periods,  has  always 
given  an  irreproachable  negative  result, 
and  there  are  no  certain  indications  of 
syphilis  present,  either  anamnesically  or 
clinically,  that  the  negative  result  of  the 
reaction  may  be  considered  diagnostically. 
Otherwise  it  cannot  in  any  way  influence 
the  treatment  of  the  practitioner,   either 

9 


THE  THERAPY  OF  SYPHILIS 

with  regard  to  prognosis  or  therapy,  as 
we  know  that,  even  when  syphiUtic  symp- 
toms are  manifest,  a  negative  result  of  the 
Wassermann  reaction  is  not  always  ex- 
cluded. In  my  opinion,  it  is  incorrect  that 
specific  treatment,  and  respectively  its  dura- 
tion and  intensity,  should  be  undertaken 
under  the  constant  control  of  the  Wasser- 
mann reaction,  its  effect  and  duration  being 
made  dependent  upon  the  occasional  result 
of  the  Wassermann  test,  as  is  done  by  some 
authors.  For,  according  to  my  researches, 
the  result  of  the  Wassermann  reaction  may 
often  fluctuate  backwards  and  forwards 
during  a  mercurial  cure. 

Besides  these  results,  which  are  valuable 
for  modern  mercurial  specific  therapy,  a 
whole  series  of  other  important  questions 
have  been  explained  by  syphilitic  research, 
or  their  solution  has  been  approached  very 
closely,  and  of  these  I  will  briefly  mention 
a  few.  Finger  and  Landsteiner,  Neisser 
and  Hoffmann  succeeded  in  proving  the 
infectiousness  of  gummata  from  observa- 

10 


THE  THERAPY  OF  SYPHILIS 

tions  on  animals.  Finger  and  Landsteiner, 
Neisser,  Tomasczewski,  Uhlenhuth,  and  I 
were  able,  by  animal  experiment,  to  con- 
tradict the  dogma  of  absolute  and  per- 
manent immunity  set  up  by  Ricord,  which 
a  single  attack  of  specific  infection  is  sup- 
posed to  bestow,  but  which,  on  the  ground 
of  clinical  observations,  had  appeared  doubt- 
ful to  some  of  his  contemporaries  and  also 
to  many  later  teachers.  Questions  of  in- 
dividual prophylaxis  were  also  touched 
upon,  and  enabled  us  to  recognise  a  good, 
but  not  absolutely  certain,  protection  against 
specific  infection  in  the  administration  of 
the  30  per  cent,  calomel  salve  (Metsch- 
nikoff  and  Roux) .  By  means  of  comprehen- 
sive serological  examinations,  the  accuracy 
of  the  law  of  Colle  and  Profata  was  de- 
termined by  Bruck,  Boas,  Blumenthal, 
Michaelis,  the  author,  and  others. 

The  triumph  of  syphilitic  research,  how- 
ever, consisted  in  its  being  the  basis  of  the 
modern  chemotherapy  of  syphilis. 


II 


THE  CHEMOTHERAPY  OF  SYPHILIS 

I.  ATOXYL. 

The  constitution  of  this  preparation,  which 
was  originally  described  as  meta-arsenic 
acid  anilide,  was  first  explained  by  P.Ehrlich 
and  Bertheim.  They  proved  that  by  heat- 
ing the  arsenic  acid  anilin,  under  a  base 
corresponding  to  the  sulphanilic  acid 
presentation,  para  -  amino  -  phenyl  -  arsenic 
acid  is  formed.  This  acid  is  very  difficult 
to  dissolve  in  water  (i  :  255)  and  by  other 
usual  methods  of  solution,  but  will  dissolve 
without  decomposing  in  caustic  and  car- 
bonic acid  alkalies.  By  dissolving  in  the 
estimated  quantity  of  alcohol,  the  mono- 
sodium  salt,  ^-aminophenylarsenic  acid, 
atoxyl  is  formed,  the  constitution  formula 

12 


THE  CHEMOTHERAPY  OF  SYPHILIS 

of  which  is  given  as  follows  by  Ehrlich 
and  Bertheim  : 


\//OH  +  4H20 
AsfO 
^ONa 


The  crystalline  watery  content  is  not  con- 
stant, but  instead  varies  with  the  manner 
of  preparation,  and  the  condition  of  crystal- 
lisation thus  caused. 

Atoxyl  is  a  crystalline  powder  without 
either  colour  or  smell,  with  a  cool,  weakly 
saline  taste.  On  heating  it  decomposes 
slowly,  gradually  assuming  a  brown  colour 
without  melting.  It  is  soluble  in  4-3  parts 
water  at  20°  C.  The  aqueous  solution 
saturated  at  this  temperature  contains 
i8*8  per  cent,  of  atoxyl.  The  solubility 
in  water  is  greatly  increased  by  a  heightened 
temperature.  It  is  very  difficult  to  dissolve 
atoxyl  in  alcohol.  The  solutions  assume 
a  browoiish-yellow  colour  if  they  stand   in 

13 


THE  THERAPY  OF  SYPHILIS 

the  air  and  light,  and  similarly  if  they  are 
boiled  for  long,  when  they  lose  their  curative 
power,  and  become  toxic  instead.  If  the 
solution  is  to  be  sterilised,  it  should  be 
heated  in  sterile  vessels  for  two  minutes 
at  70°  to  80°  C,  or  it  should  be  filtered  after 
Uhlenhuth's  method,  by  means  of  Berke- 
feld's  bougies.  In  this  way,  a  sterile  prep- 
aration which  is  perfectl}^  irreproachable 
is  obtained. 

The  aqueous  solution  has  a  weakly  acid 
reaction.  If  it  is  transposed  with  diluted 
acids,  then  the  atoxylic  acids  will  be  pre- 
cipitated in  thick  white  flakes,  which 
dissolve  ver}^  easily  in  the  overflow,  but 
not  in  that  of  acetic  acid. 

F.  Blumenthal  was  the  first  to  employ 
the  new  drug  in  medical  practice,  in  1902. 
By  means  of  valuable  pharmacological 
researches,  he  proved  the  relative  non- 
toxicity  of  the  preparation,  and  drew 
attention  to  its  favourable  qualities.  Ac- 
cording to  the  reports  of  F.  Blumenthal, 
atoxyl  is  forty  times  less  toxic  than  Fowler's 

14 


THE  CHEMOTHERAPY  OF  SYPHILIS 

solution.  Further,  he  considers  this  prep- 
aration has  the  advantage  over  Fowler's 
solution  and  other  arsenic  preparations,  in 
that  the  arsenic  from  this  atoxyl,  although 
bound  fast  to  the  benzol  nucleus,  is  split 
up  in  the  organism,  and  so  acts  in  statu 
nascendi.  The  researches  of  Blumenthal 
and  Jakoby  place  the  principal  action  of 
atoxyl  in  the  blood,  where  it  either  acts 
directly  by  splitting  up  the  arsenic  acids, 
or  may  appear  catalytically  in  function, 
while  acting  upon  such  in  the  cure  of 
important  processes. 

It  was  through  the  English  ph^^sician 
W.  Thomas  that  atoxyl,  which  had  already 
been  found  to  be  tolerated  in  the  treat- 
ment of  diseases  of  the  blood  and  of 
the  nervous  system,  as  well  as  in  various 
cutaneous  affections,  was  introduced  into 
the  therapy  of  trypanosome  diseases  (1905). 
Thomas  and  Breinl  obtained  excellent 
results  in  the  experimental  infection  of  rats, 
mice,  rabbits,  etc.,  with  the  trypanosomes 
of   surra,    nagana,    sleeping   sickness,    etc. 

15 


THE  THERAPY  OF  SYPHILIS 

The  results  of  the  experiments  of  Mesnil, 
Nicolle,  and  Ehrlich  were  less  favourable ; 
independently  of  Thomas,  they  adminis- 
tered atoxyl  to  animals  infected  by  the 
tsetse  fly,  surra  and  mal  de  caderas.  Atoxyl, 
recommended  by  Thomas,  was  further  tried 
with  advantage  by  Kopke,  Broden,  Rod- 
hain,  and  others  in  the  treatment  of  sleep- 
ing sickness ;  but  it  was  Robert  Koch 
who  first  carried  out  a  systematic  and 
purposeful  atoxylic  cure,  when  the  material 
at  hand  was  on  a  large  scale.  Amongst 
other  things,  R.  Koch  was  able  to  prove 
that,  eight  hours  after  the  injection  of 
atoxyl,  the  trypanosomes  had  already  dis- 
appeared from  the  lymphatic  glands  and 
from  the  blood.  Moreover,  with  the  dis- 
appearance of  the  trypanosomes  from  the 
lymphatic  glands,  a  distinct  improvement 
took  place  in  the  patient's  condition. 

Instigated  by  the  reports  which  had  been 
published,  and  particularly  by  Koch's 
favourable  results,  Uhlenhuth  commenced 
some  experiments  at  the  Imperial  Health 

i6 


THE  CHEMOTHERAPY  OF  SYPHILIS 

Bureau,  Berlin,  in  1906,  which  consisted 
first  in  treating  dourine  disease  with  atoxyl. 

As  has  been  reported  by  Uhlenhuth  and 
his  collaborators  Hiibener,  Woithe,  and 
Bickel,  the  results  of  the  protective  and 
curative  experiments  undertaken  in  this 
direction  were  favourable. 

Further,  the  authors  recorded  that  certain 
considerations  had  led  them  to  try  atoxylic 
treatment  in  other  protozoal  diseases  also. 
The  opinion  laid  down  by  Schaudinn,  that 
many  spirochaetes  represent  special  stages 
of  development  of  trypanosomes,  caused 
them  first  of  all  to  try  atoxyl  in  spirillosis 
of  fowls. 

The  exciter  of  this  disease  is  the  5. 
gallinarum,  which  was  discovered  by  Mar- 
choux  and  Salimpeni  at  Rio  de  Janeiro, 
in  1903.  The  disease,  which  frequently 
sets  in  as  septicaemia  with  a  fatal  result, 
begins  with  high  fever  and  diarrhoea.  The 
animals  soon  become  somnolent,  and  some- 
times succumb  from  paralysis  and  also  from 
spasms.     If  fowls  are  infected  with  blood 

17  B 


THE  THERAPY  OF  SYPHILIS 

containing  spirochsetes,  the  parasites  can 
generally  be  detected  in  the  circulation 
on  the  second  day  after  infection ;  they 
increase  rapidly  up  to  the  fourth  to  sixth 
day,  when  they  can  be  found  in  the  blood  in 
great  convoluted  colonies.  The  crisis  sets 
in  on  the  seventh  to  ninth  day ;  the 
spirochaetes  disappear  spontaneously  from 
the  circulation,  and  the  animals  are  then 
immune,  if  they  do  not  succumb  to  the 
disease.  A  natural  immunity  is  obviously 
rare. 

Here,  also,  the  authors  succeeded  in 
proving  in  an  absolutely  trustworthy  manner 
that  atoxyl  exercises  a  protective  and  cura- 
tive action  in  spirillosis  of  fowls  ;  that  it 
is  capable  of  destroying  the  spirochsetes  in 
the  blood  of  the  diseased  fowls  and  of 
causing  their  disappearance. 

Uhlenhuth,  Gross,  and  Bickel  conclude 
their  communications,  which  appeared  in 
No.  4  of  the  Deutschen  Medizinischen  Woch- 
enschrift,  January  24,  1907,  with  the  follow- 
ing words  :  *'  As  atoxyl  has  a  destructive 

18 


THE  CHEMOTHERAPY  OF  SYPHILIS 

action  on  the  most  varied  trypanosomes, 
it  is  easy  to  reflect  that  it  may  develop  a 
similar  action  to  that  of  the  S.  gallinarum 
on  various  other  spirochaetes.  Appropriate 
experiments  with  the  spirochsetes  of  re- 
lapsing fever  and  of  syphilis  are  in  progress, 
the  positive  result  of  which  would  be  of 
practical  importance  in  combating  these 
diseases/' 

It  was  soon  possible  to  report  on  the 
results  of  researches  of  this  description. 
The  experimental  work  of  Uhlenhuth  and 
his  collaborators  in  relapsing  fever  of  mice 
and  rats  did  not,  it  is  true,  enable  one 
to  come  to  a  definite  conclusion  as  to  the 
efficacy  of  these  preparations  in  this  disease, 
on  account  of  their  toxicity  for  these 
animals  ;  but,  on  the  other  hand,  the  ex- 
periments undertaken  by  Glaubermann 
at  Moscow,  at  the  instigation  of  Uhlenhuth, 
in  Russian  relapsing  fever,  were  on  the 
whole  favourable.  It  seemed  most  impor- 
tant to  Uhlenhuth,  however,  that  atoxyl 
should  be  tried  in  the  spirochaete  disease 

19 


THE  THERAPY  OF  SYPHILIS 

of    most    frequent    occurrence  —  namely, 
syphilis. 

As  long  ago  as  December,  1906,  Uhlen- 
huth,  with  Hoffmann,  Roscher,  and 
Weidanz,  had  endeavoured  to  obtain  a 
definite  answer  to  the  question  whether 
atoxyl  exercised  a  direct  influence  on  the 
process  of  specific  disease.  In  S3^philis  of 
apes,  as  well  as  of  rabbits  (disease  of  the 
cornea)  the  authors  actually  observed  a 
noticeable  prophylactic  and  curative  effect 
of  atoxyl.  Equally  good  results  were  ob- 
tained soon  after  by  A.  Neisser,  who  also 
proved,  by  means  of  experiments  on  apes, 
that  energetic  treatment  with  atoxyl,  which 
is  best  when  administered  in  large  single 
doses,  has  a  very  marked  influence  on 
syphilis.  Therapeutic  experiments  on 
human  subjects  at  the  Lesser  Clinique,  at 
Uhlenhuth's  suggestion,  were  extraordin- 
arily successful  with  the  correct  dosage, 
after  having  failed  at  first  when  the  dose 
administered  was  too  small.  The  results 
of  this  treatment  are  reported  in  detail 

20 


THE  CHEMOTHERAPY  OF  SYPHILIS 

in  a  work  by  Uhlenhuth,  Hoffmann,  Roscher, 
and  Weidanz.  Further,  Salmon,  Lassar, 
Hallopeau  and  others  shortly  afterwards 
recorded  very  successful  curative  results 
obtained  in  human  s^^philis  with  atoxyl. 
E.  Lesser  spoke  very  favourably  of  atox^dic 
treatment  of  specific  disease,  which  he  re- 
garded as  equal  to  the  customary  doses  of 
calomel  in  rapidity  of  result.  Of  further 
authors  who  tested  the  therapeutic  effect 
of  atoxyl  on  syphilis,  and  generally  obtained 
good  results  with  it,  I  should  like  to  men- 
tion Hoffmann,  von  Zeissl,  Lesser,  Nagel- 
schmidt,  Finger,  Moses,  Darier,  Heuck, 
Balzer,  Rouviere,  Kreibich  and  Kraus, 
Scherber,  Rapiport,  and  others. 

If  we  compile  a  resume  from  these  com- 
munications, references,  and  clinical  ob- 
servations in  specialist  literature,  then, 
according  to  Salmon,  the  favourable  effect 
of  atoxyl  in  syphilis  is  shown  : — 

I.  As  regards  the  Constancy  of  the  Results. 
— The  favourable  curative  effect  appeared 
in    all    stages    of    syphilis — viz.,  primary, 

21 


THE  THERAPY  OF  SYPHILIS 

secondary,  and  tertiary  —  and  was  most 
brilliant  in  malignant  forms. 

2,  As  regards  the  Rapidity  of  the  Action 
of  the  Drug. — After  a  few  injections,  chancres 
diminish  and  are  absorbed,  the  hardness 
often  disappears  remarkably  quickly.  Fresh 
roseola,  maculo-papulous  exanthema,  im- 
petigo capitis  disappear  after  ten  to  four- 
teen days,  psoriasis  palmarum  after  twelve 
days.  The  exanthema  becomes  paler  until 
it  is  invisible.  Papules  lose  their  redness, 
and,  with  the  absorption  of  the  plastic 
exudation,  flattening,  and  typical  brown- 
ing (regressive  metamorphosis)  is  evident. 
Ulcerations  close  and  skin  over,  annular 
syphilides  dry  up,  and  gummatous  infiltra- 
tions yield  to  the  treatment  in  a  similar 
way.  Papules,  plaques,  tuberculous  syphi- 
lides, tertiary  ulcers,  diminish  rapidly  and 
generally  heal  over.  The  headache,  which 
is  characteristic  of  syphilis,  often  ceases 
surprisingly  rapidly  (eighteen  hours)  after 
the  first  injection,  the  dysphasia  and 
dysphagia   of   angina   syphilitica   decrease 

22 


THE  CHEMOTHERAPY  OF  SYPHILIS 

after  two  to  three  days.  According  to 
Darier  and  others,  iritis  syphilitica  can  also 
be  very  favourably  influenced  by  treatment 
with  atoxyl. 

Cases  which  are  refractory  to  mercurial 
treatment,  or  are  only  slightly  influenced 
by  it,  such,  especially,  as  cases  of  syphilis 
ulcerosa  prsecox  (malignant  syphilis) ,  gener- 
ally react  rapidly  and  promptly  to  atoxyl. 

3.  ^5  regards  the  Favourable  Effect  on  the 
General  Condition. — The  patients  feel  well, 
and  nearl}^  all  of  them  increase  considerably 
in  weight. 

Unfortunately  atoxyl  did  not  subse- 
quently fulfil  the  hopes  which  had  been 
centred  on  it  for  the  therapy  of  syphilis. 
The  observations  on  atoxylic  resistance,  to 
which  Ehrlich  first  referred,  and  the  prac- 
tical experience  gained  in  combating  syphilis, 
showed  that  favourable  results  could  only 
be  obtained  with  large  doses  of  atoxyl. 
These  doses,  however,  approached  pretty 
closely  to  toxic  ones,  and  undoubtedly  there 
was  danger  that  with  them  the  limit  of 

23 


THE  THERAPY  OF  SYPHILIS 

isotonicity  of  the  preparation,  which  varies 
in  individual  cases,  might  be  exceeded. 
That  this  was  actually  done  in  the  thera- 
peutic administration  of  atoxyl  was  proved 
by  observations  of  injury  to  the  central 
nervous  organs  (transitory  visual  disturb- 
ances extending  to  blindness,  and  respec- 
tively total  atrophy  of  the  visual  nerves).^ 

In  order  to  prevent  relapses,  it  was 
necessary  to  repeat  the  application  at  short 
intervals,  and  thus  the  danger  of  over- 
dosage was  still  further  increased.  After 
the  cases  of  blindness  which  were  first 
observed  in  the  treatment  of  sleeping  sick- 
ness had  been  reported,  naturally  the  general 
administration  of  atoxyl  in  syphilis  had 
to  cease.  Uhlenhuth  himself  was  the  first 
to  demand  this,  and  wished  to  reserve 
the  employment  of  atoxyl  for  those  cases 
which    had    proved    refractory    to    mer- 

^  Schanz  assumes  that  this  process  in  the  visual 
nerves  must  have  its  origin  far  from  the  bulbus,  as 
for  a  long  time  the  ophthalmoscope  gave  a  negative 
result,  even  if  the  visual  disturbances  were  already 
extensive. 

24 


THE  CHEMOTHERAPY  OF  SYPHILIS 

cury,  or  had  been  only  slightly  influenced 
by  it. 

In  all  the  cases  of  visual  disturbance 
observed,  it  was  possible  to  regularly 
build  up  the  distinct  progress  of  this 
disease,  and  give  sharply-defined  pictures 
of  the  disease  and  development  of  atoxylic 
blindness  respectively.  According  to 
Sowade,  its  individual  phases  were  pre- 
sented as  follows  : — 

1.  Beginning  with  ''  cloudiness  ''  or  **  a 
veil  before  the  eyes.'' 

2.  Intense  diminution  of  the  visual  power 
within  a  few  days  and  weeks. 

3.  At  first  there  were  no  changes  in  the 
fundus  oculi,  and  often  it  was  only  after 
months  that  there  was  perceptible  atrophy 
of  the  papilla  of  the  optic  nerve,  without 
previous  neuritic  phenomena.  Contraction 
of  the  vessels  of  the  retina. 

4.  Frequent  maintenance  of  the  normal 
papillary  reaction. 

5.  As  a  rule,  impossibility  of  arresting 
the  advance  of  the  affection. 

25 


THE  THERAPY  OF  SYPHILIS 

By  means  of  experimental  researches  on 
rabbits  and  dogs,  Birch  -  Hirschf  eld  and 
Koster  proved  that  if  atoxyl  was  adminis- 
tered for  a  long  time  until  the  death  of  the 
animal,  the  optic  nerve  microscopically 
showed  disintegration  of  the  medullary 
sheath  over  the  entire  transverse  section. 

It  was  thought  at  first  that  these  toxic 
secondary  effects  of  atoxyl  were  due  to 
chemical  impurities,  and  attributable  to 
the  German  preparation.  A  change  in  the 
production  of  the  preparation,  however, 
did  not  result  in  any  noticeable  diminution 
of  its  toxicity. 

In  order  that  the  undoubtedly  favourable 
specific  action  of  atoxyl  in  the  treatment  of 
trypanosome  diseases  and  syphilis  need  not 
have  to  be  abandoned  altogether,  especially 
in  cases  in  which  Hg  and  other  drugs  fail, 
various  combinations  were  tried  of  atoxyl 
with  other  preparations  or  alterations  of 
the  chemical  structure  of  atoxyl,  which  were 
supposed  to  be  less  toxic  in  their  effects. 
Thus  we  have : — 

26 


THE  CHEMOTHERAPY  OF  SYPHILIS 

II.  ARSACETIN  (EHRLICH), 

which  was  obtained  from  atoxyl  by  chemical 
changes.  It  is  the  salts  of  sodium  of  the 
acetyl  combination  of  ^-aminophenylar- 
sanilic  acid  of  sodium. 

Arsacetin  is  represented  by  a  white 
powder ;  the  crystalline  water  contains  three 
to  four  molecules,  and  dissolves  easily  in 
cold  water  at  lo  per  cent.,  in  hot  at  30  per 
cent.  It  does  not  decompose  on  boiling, 
and  has  been  proved  to  be  constant  through- 
out (according  to  So  wade),  even  when  heated 
in  an  autoclave  for  an  hour  and  at  130°  C. 

It  has  been  pharmacologically  deter- 
mined by  Ehrlich,  Browning,  Uhlenhuth, 
and  Salmon  that  healthy,  as  well  as  diseased, 
animals  can  tolerate  much  higher  doses  of 
arsacetin  than  they  can  of  atoxyl. 

Neisser  states  that  it  has  been  proved 
experimentally  that,  in  the  trypanosome 
and  spirilla  diseases  of  various  animals, 
arsacetin  is  at  any  rate  found  to  be  quite 
as  good  as  atoxyl. 

37 


THE  THERAPY  OF  SYPHILIS 

Neisser  and  the  few  teachers  who  have 
tested  this  preparation  therapeutically,  have 
obtained  a  good  effect  on  the  diseased 
syphilitic  tissue  with  it,  similar  to  that  of 
atoxyl.  Here,  again,  the  tertiary  forms 
of  the  disease,  as  well  as  malignant  syphilis, 
appeared  to  be  specially  favourably  in- 
fluenced by  the  drug.  The  experience  of 
Heymann  and  Sowade,  however,  showed 
that,  in  the  majority  of  cases,  the  effect  of 
mercury  was  undoubtedly  more  certain 
and  durable.  Soon  after  the  employment 
of  arsacetin,  reports  came  to  hand  from 
different  sources  of  ''  considerable  phe- 
nomena of  intoxication,"  such  as  headache, 
nausea,  vomiting,  giddiness,  abdominal  pain, 
shooting  pains  in  the  extremities,  nephritis, 
and  finally  visual  disturbances  (Heymann, 
Klemperer,  Sowade,  etc.),  from  which  it 
appeared  that  arsacetin,  especially  with 
regard  to  a  toxic  action  on  the  optic  nerve 
(in  Africa,  5  to  10  per  cent,  atrophy  of  the 
optic  nerve),  was  more  poisonous  than 
atoxyl    (Jenssen,    Oppenheim,    Paderstein, 

a8 


THE  CHEMOTHERAPY  OF  SYPHILIS 

Ruele,  Hammer,  Pflughoft,  Borcher). 
Further,  it  seemed,  as  Uhlenhuth  reported 
at  the  Colonial  Congress,  1910,  according 
to  the  records  of  Feldmann,  that  arsacetin 
exercised  a  toxic  action  on  the  auditory 
nerves.  In  Africa,  out  of  fifty-one  patients 
treated  with  arsacetin,  nine  became  blind 
and  two  simultaneously  deaf. 

As  Heinrich  has  cited,  Ehrlich  himself 
is  of  opinion  that  arsacetin  possesses  no 
advantages  over  atoxyl  in  a  number  of 
diseases,  especially  those  of  syphilis  and 
sleeping  sickness,  which  ''  to  a  certain  ex- 
tent are  difficult  to  steriHse.''  On  account 
of  the  threatened  danger  to  the  eyes, 
Ehrlich  no  longer  recommended  it. 

III.    ATOXYLATE     OF     MERCURY    (UHLEN- 
HUTH) (P-AMINOPHENYLARSONATE  Hg). 

At  the  Imperial  Health  Bureau,  Berlin, 
Uhlenhuth,  Hiibener  and  Woithe  obtained 
good  results  in  dourine,  in  experiments 
carried  out  by  the  combined  application 
of    atoxyl    and    sublimate.     Further,    the 

29 


THE  THERAPY  OF  SYPHILIS 

therapeutic  experiments  in  relapsing  fever, 
reported  by  Manteufel,  showed  that  mer- 
cury had  a  certain  therapeutic  effect  on 
this  spirochaete  disease  in  colloid  form. 
On  the  basis  of  these  results,  and  in  con- 
sideration of  the  fact  that  mercury  is  known 
empirically  to  act  organically  on  syphilis 
and  respectively  on  the  spirochsetes,  the 
exciters  of  this  disease  (Uhlenhuth  and 
Manteufel),  Uhlenhuth,  at  a  meeting  of  the 
Association  of  Internal  Medicine,  Berlin, 
June  24,  1907,  proposed  that  a  combination 
of  atoxyl  and  mercury  should  be  used  for 
the  treatment  of  S3^philis.  In  trypanosome 
diseases,  treatment  with  these  two  drugs 
had  already  been  recommended  by  Moore, 
Nierenstein,  and  Todd. 

Soon,  as  the  results  of  experiments  on 
animals  made  with  a  new  atoxylic  prepara- 
tion brought  out  by  the  United  Chemical 
Works,  Charlottenberg,  from  Uhlenhuth's 
formula,  Uhlenhuth  and  Manteufel  were 
able  to  record  good  results  obtained  with 
this  new  drug,  atoxylate  of  mercur}^,  which 

30 


THE  CHEMOTHERAPY  OF  SYPHILIS 

promised  to  be  of  practical  importance  in 
the  treatment  of  syphilis. 

Both  authors  first  made  researches  with 
atoxylate  of  mercury  by  experimentally 
infecting  rats  with  relapsing  fever.  Al- 
though in  themselves  apparently  very  un- 
suitable for  such  treatment,  as  they  tolerate 
atoxyl,  and  mercury  especially,  very  badly, 
nevertheless,  it  was  distinctly  possible  to 
recognise  the  antiparasitic  qualities  of  the 
preparation  from  the  experiments. 

Further  experiments  made  on  spiro- 
chaetic  septicaemia  of  fowls  proved  that 
atoxylate  of  mercury  actually  exercised 
a  very  energetic  action  on  the  spirochaetes. 

After  these  preliminary  exploratory  ob- 
servations, the  authors  proceeded  to  in- 
fluence experimental  syphilis  with  atoxylate 
of  mercury  therapeutically.  The  effects  ob- 
served in  corneal  syphilis  of  rabbits  entirely 
confirmed  the  results  obtained  in  the  study 
of  spirochaetosis  of  fowls.  Uhlenhuth  and 
I  succeeded  in  completely  curing  three 
large  typical  syphilitic  ulcers  in  ten  and 

31 


THE  THERAPY  OF  SYPHILIS 

eighteen  days  respectively,  two  being  scrotal 
ones  in  rabbits.  Later,  we  were  able  to 
confirm  these  results  on  a  large  quantity  of 
rabbits.  We  simultaneously  made  the  obser- 
vation that  even  as  soon  as  twenty-four  hours 
after  the  first  adequate  dose  no  spirochsetes 
at  all,  or  only  very  few,  could  be  found  in  the 
diseased  material,  and  that,  after  a  further 
twenty-four  to  twenty-six  hours,  they  had 
entirely  disappeared. 

It  is  evident  from  the  above,  that  in  these 
healing  processes  we  have  to  do  with  a 
specific  action  of  this  preparation  on  the 
spirochaetes  themselves,  as  was  already 
shown  by  Uhlenhuth  and  others  in  their 
experiments  on  fowls  suffering  from  spiro- 
chaetes ;  for  that  tissue  was  first  influenced 
therapeutically  which  contained  large  quan- 
tities of  spirochaetes.  As  Uhlenhuth  and 
I  first  showed,  these  are  typical  forms  of 
syphilis  induced  experimentally  in  rabbits. 
This  drug  reacts  most  markedly  on  syphi- 
litic indurations — the  sclerotic,  hard  tissue, 
characteristic   of  primary  specific   disease. 

32 


THE  CHEMOTHERAPY  OF  SYPHILIS 

When  induced  in  rabbits,  this  tissue  con- 
tains spirochaetes  in  genuinely  pure  culture.^ 
After  one  or  a  few  injections  (with  small 
doses)  the  sclerotic  tissue  disappears  alto- 
gether, no  spirochaetes  can  be  discovered, 
the  scrotal  tissue  has  apparently  again 
become  normal,  and  the  former  deep  ulcers 
are  healing  smoothly  under  good  granula- 
tion formation.  The  specific  reactions  be- 
tween the  5.  pallida  and  the  arsenic  and 
mercurial  preparations,  as  I  mentioned 
at  the  beginning,  give  us  visible  proof 
of  the  irritant  nature  of  the  spirochaete  in 
human  syphilis,  as  well  as  that  of  rabbits 
(Uhlenhuth  and  Mulzer). 

After  a  few  exploratory  preliminary  ex- 
periments on  human  subjects,  which  gave 
similar  results  to  the  successful  ones  on 
animals,     Uhlenhuth    recommended    that 

^  It  is  a  mistake  if  Hata,  in  the  Ehrlich  book  "  On 
the  Chemotherapy  of  Spirilloses/'  asserts  that  we 
recommended  syphiloma  of  the  scrotum,  which  con- 
sists of  loose  myxomatous  tissue  and  also  contains 
a  great  quantity  of  spirochsetes,  for  the  purpose  of 
testing  chemotherapeutical  experiments. 

33  C 


THE  THERAPY  OF  SYPHILIS 

atoxylate  of  mercury  should  be  employed 
for  the  therapy  of  syphilis.  This  new 
preparation  was  first  used  extensively  in 
therapeutics  by  Miekley  at  the  Lesser 
Qinique. 

The  administration  of  the  drug  was 
as  follows  :  It  was  begun  with  doses  of 
0-05  gramme  twice  in  the  first  week,  and 
then  continued  with  o*i  gramme  per  week 
until  a  total  amount  of  0*5  gramme  had 
been  given  (with  women,  0*48  gramme). 

The  results  obtained  with  these  patients 
were  well  worthy  of  notice.  Cases  of 
syphilis  in  various  stages  were  treated 
with  atoxylate  of  mercury. 

It  was  specially  interesting  to  notice 
that  frequently  even  after  0*05  gramme,  or 
at  most  after  o-i  gramme,  the  papu- 
lous syphilides  began  to  dissolve,  the  in- 
filtrations especially  disappearing  very 
rapidly.  ''  After  the  third  injection,  as 
a  rule,  all  that  was  left  of  the  papulous 
exanthemata  was  the  pigment  residue 
without    any    infiltration    being    clinically 

34 


THE  CHEMOTHERAPY  OF  SYPHILIS 

evident,"  Miekley  reports.  He  was  further 
able  to  testify  to  a  markedly  favourable 
effect  of  hydrarg.  atoxyl  in  malignant 
syphilis,  and  in  the  ulcerous  and  gummatous 
cutaneous  processes  of  tertiary  syphilis. 
The  secondary  effects — in  some  cases  stoma- 
titis and  albuminuria — were  very  slight, 
and  easily  disappeared  when  the  drug  was 
stopped.  According  to  a  report  of  E.  Les- 
ser's  in  the  Charite  Annates,  1910,  up  to 
that  time  127  cases  had  been  treated  in  the 
Lesser  Clinique  with  hydrarg.  atoxyl.  ''  The 
result  on  the  whole  was  good,  despite  the 
relatively  small  dose,  the  phenomena  gener- 
ally retrogressed  rapidly,  and  often  dis- 
appeared after  the  first  injection.  The  effect 
of  hydrarg.  atoxyl  seemed  to  be  specially 
favourable  in  galloping  syphilis."  Lesser 
states  that  out  of  these  127  cases,  16  relapses 
came  under  observation  after  the  course  of 
a  few  months.  The  result  of  the  Wasser- 
mann  reaction  with  13  men  was  positive 
once  and  negative  12  times  ;  with  17  women, 
12  times  positive  and  5  times  negative. 

35 


THE  THERAPY  OF  SYPHILIS 

Blaschko  also  mentions  good  results  he 
obtained  with  atoxylate  of  mercury  ;  only 
he  gave  larger  doses  than  Lesser,  as 
he  extended  them  up  to  ten  injections. 
The  principal  secondary  effect  Blaschko 
noticed  was  unusual  pain  during  the  in- 
jection, such  as  is  not  common  to  other  mer- 
curial preparations.  He  attributed  this  to 
the  suspension  of  the  preparation  in  olive  oil. 

Soon  afterwards  Fabry  briefly  recorded 
very  good  curative  results  in  syphilis  with 
atoxylate  of  mercury ;  similar  experiences 
were  communicated  by  Lambkin.  A  more 
detailed  account,  completing  Fabry's  report, 
was  given  by  Boethke  in  his  inaugural 
dissertation. 

Bergarth's  results  were  less  favourable, 
despite  the  fact  that  he  injected  larger  doses 
than  teachers  had  done  previously.  Atoxy- 
late of  mercury  failed  especially  in  his  cases 
of  syphilis  gravis  and  maligna.  According 
to  the  experience  of  this  author,  atoxylate 
of  mercury,  in  the  doses  which  were  formerly 
administered   in   syphilitic    processes,    did 

36 


THE  CHEMOTHERAPY  OF  SYPHILIS 

not  appear  to  have  the  effect  of  salicylic 
acid  mercury.  Neither  could  this  author 
detect  any  kind  of  increased  secondary 
effects.  Zieler  is  said  to  have  observed  that 
patients,  who  were  first  treated  with  atoxy- 
late  of  mercury,  and  were  then  given  grey 
oil,  suffered  less  from  the  kidneys. 

IV.  HECTINE. 

Mouneyrat  called  a  ''  benzolsulphonepara- 
minophenylarsenate  of  sodium,"  which  he 
produced  syntheticall}^  shortly  ''  hectine.'' 
This  body  is  supposed  to  be  more  active 
than  the  other  arsenic  preparations,  and 
less  toxic  than  atoxyl.  The  injurious 
optical  secondary  effects  are  also  supposed 
to  be  absent.  According  to  Balzer  and 
Mouneyrat,  hectine  is  specially  effective  in 
the  secondary  period  of  syphilis,  in  the 
tertiary  stage  with  gummata  and  ulcers, 
and  in  very  obstinate  cases,  which  require 
prolonged  treatment. 

Hectine  can  be  administered  in  a  daily 
dose  of  20  centigrammes,  and  continued  for 

37 


THE  THERAPY  OF  SYPHILIS 

about  twenty  to  thirty  days.  From  his 
experience,  Hallopeau  considers  fifteen 
days'  local  treatment  of  the  primary  affec- 
tion, combined  with  about  thirty  days' 
general  treatment,  is  sufficient  to  cure 
syphilis.  Certainly  this  must  be  com- 
menced at  once,  if  the  presence  of  the 
S.  pallida  has  been  detected  in  any  form  of 
illness  suspected  of  being  a  primary  affec- 
tion. 

At  the  present  time  I  am  not  aware  that 
these  statements  of  Hallopeau's  have  been 
further  tested. 

According  to  the  communications  of 
Neisser,  hectine  is  said  also  to  induce 
optical  disturbances. 

V.  SOAMIN. 

At  the  end  of  1907,  an  atoxylic 
preparation,  ''  soamin "  (sodii  ^-amino- 
phenylarsonas)  was  employed  in  England, 
which  was  supposed  to  be  absolutely  with- 
out toxic  secondary  effects.  It  was  said 
to  have  a  more  constant  arsenic  content 

38 


THE  CHEMOTHERAPY  OF  SYPHILIS 

than  atoxyl,  and  was,  therefore,  capable  of 
being  administered  with  greater  certainty 
than  the  inconstant  atoxyl.     So  far,  there 
are  very  few  reports   of  the   therapeutic 
application  of  this  preparation  in  syphilis 
and  other  diseases ;  in  reality,  it  is  not  dis- 
tinguishable from  atoxyl,  and,  like  it,  has 
given   rise   respectively   to   blindness   and 
atrophy  of  the  optic  nerve  in  isolated  cases 
(Lambkin,  Pritchard,  Johnston  and  others). 
As  we  have  seen,   the  correct  chemical 
constitution  of  atoxyl  was  first  recognised 
by  Paul  Ehrlich,  together  with  its  thera- 
peutic application  in  trypanosome  diseases. 
Starting  from  this,  the  purposeful  and  inde- 
fatigable effort  of  this  researcher  was  to  pre- 
vent ''  the  uncertain  and  doubtful  action  of 
atoxyl  in  trypanosome  diseases  by  means 
of  appropriate  alterations  of   the  arsenic- 
fast  residue,''  and  so  ''procure  a  reliable 
arsenic  drug  of    which  there  could  be  no 
doubt."     In  other  words,  Ehrlich  set  him- 
self the  task  of  finding  curative  substances 
for  the  treatment  of  trypanosome  diseases 

39 


THE  THERAPY  OF  SYPHILIS 

in  which  the  parasitotropic grou-^s — i.e.,  those 
which  destroy  the  parasites — are  increased, 
while,  on  the  other  hand,  the  organotropic, 
which  have  an  injurious  effect  on  the  vital 
organs,  are  diminished  as  much  as  possible. 

The  toxic  organotropic  action  of  atoxyl 
and  of  arsacetin  was  attributed  by  Ehrlich 
to  the  fact  that  these  preparations  contain 
a  quinquevalent  arsenical  residue.  By  con- 
tinuously reducing  this  substance,  Ehrlich 
was  able  to  form  the  arsenic  combination 
in  such  a  way  that  a  trivalent  arsenic 
residue  was  substituted,  and  therefore,  in 
his  opinion,  this  new  preparation  must  be 
less  toxic  and  distinctly  parasitotropic  in 
its  action. 

In  this  way,  by  means  of  chemical  syn- 
thesis, Ehrlich,  after  numerous  experiments, 
succeeded  in  obtaining 

VI.  ARSENOPHENYLGLYCIN, 

a  preparation,  which  appeared  to  possess 
in  a  high  degree  the  characteristics  Ehrlich 
had  endeavoured  to  obtain,  by  means  of 

40 


THE  CHEMOTHERAPY  OF  SYPHILIS 

comprehensive  experimental  tests.  In  con- 
sequence of  the  strong  parasitotropic  action 
of  this  preparation,  Ehrlich  hoped  to  en- 
tirely destroy  the  parasites  in  experimentally 
induced  trypanosome  diseases,  by  means 
of  a  single  adequate  application  [dosis 
efficiens  tolerata),  and  to  a  certain  extent 
to  ''  sterilise  ''  the  organism. 

Ehrlich  describes  this  new  therapeutic 
procedure  in  the  treatment  of  diseases  of 
this  kind,  as  Therapia  sterilisans  magna,  in 
contradistinction  to  the  usual  gradual  treat- 
ment with  smaller  doses,  the  administration 
of  which  was  repeated  at  shorter  intervals. 

The  chemical  constitution  formula  of 
arsenophenylglycin  is  as  follows  : 

As  =^As 

I 


\/ 

\y 

NH 

NH 

CH2 

CH2 

COONa 

COONa 

41 


THE  THERAPY  OF  SYPHILIS 

The  preparation  is  represented  by  a 
yellow  powder  easily  soluble  in  water.  It 
can  be  preserved  for  some  time  in  her- 
metically sealed  vacuum  tubes,  whereas, 
when  it  comes  in  contact  with  the  atmo- 
sphere, it  gradually  discolours,  becomes  a 
reddish-brown,  and  oxidises  into  a  more 
toxic  product. 

Uhlenhuth  reported  at  the  Colonial  Con- 
gress (October  6, 1910)  that,  from  the  reports 
of  Ulrich  and  Scherschmidt  in  Africa,  it 
appeared  that,  in  treating  sleeping  sickness 
with  arsenophenylglycin,  injurious  effects 
had  been  observed  in  numerous  cases,  which 
were  partly  of  a  threatening  nature.  These 
consisted  in  cutaneous  eruptions,  paralyses, 
emaciation,  and  in  some  cases  of  epileptic 
attacks.  The  cutaneous  eruptions,  which 
covered  the  entire  body,  were  very  un- 
pleasant, and  gave  rise  to  the  formation 
of  vesicles  and  necrosis.  Uhlenhuth  stated 
that  Scherschmidt  reported  as  specially 
unfavourable  the  fact  that,  even  after  a 
single  administration  of  i  to  2  grammes  of 

42 


THE  CHEMOTHERAPY  OF  SYPHILIS 

arsenophenylglycin  in  quite  fresh  cases, 
emaciation  and  prostration  were  observed, 
and  even  death  in  some,  a  few  days  after  the 
injection. 

Von  Raven,  who  also  observed  toxic 
secondary  effects,  specially  gave  a  warning 
against  the  employment  of  repeated  small 
doses,  as  these  are  followed  by  hyper- 
sesthesia  and  phenomena  of  intoxication. 
For  the  rest,  his  results  in  the  treatment  of 
sleeping  sickness  were  more  favourable  in 
Togo  than  they  were  in  East  Africa ;  ob- 
viouslv,  also,  the  course  of  this  disease  is 
much  slighter  in  Togo. 

On  the  recommendation  of  Ehrlich,  Alt 
for  the  first  time  administered  this  prepara- 
tion to  patients  suffering  from  mental 
disease,  idiotcy,  and  epilepsy  with  a  syphilitic 
foundation.  He  administered  this  prepara- 
tion in  a  single  concentrated  dose.  In 
accordance  with  Ehrlich' s  therapia  magna 
sterilisans,  instead  of  the  customary  gradual 
treatment  which  had  been  employed  pre- 
viously, Alt  firmly  believed  that  he  would 

43 


THE  THERAPY  OF  SYPHILIS 

be  able  to  testify  to  the  specific  action 
of  arsenophenylglycin  in  these  diseases. 
Conjointly  with  a  rapid  and  durable 
improvement  in  a  great  number  of  cases, 
he  perceived  the  disappearance,  or  at  least 
the  diminution,  of  the  positive  result  of 
the  Wassermann  reaction. 

Further  experiments  of  this  kind,  especi- 
ally in  florid  or  tertiary  syphilis,  have  not 
been  undertaken  with  arsenophenylglycin, 
or  have  not  been  published. 

On  the  occasion  of  a  post  -  graduate 
lecture,  delivered  during  the  winter  term 
of  1909-10,  Ehrlich  first  reported  that 
he  had  found  a  new  preparation,  which  in 
its  chemotherapeutical  action  surpassed 
arsenophenylglycin. 

VII.  DIOXYDIAMIDOARSENOBENZOL 
(EHRLICH- HATA,  ''606"), 

like  all  the  arsenic  preparations  already 
mentioned,  belongs  to  the  group  of 
aromatic  arsenic  combinations.  Ehrlich 
sent  it   to  Professor    Alt    in    September, 

44 


THE  CHEMOTHERAPY  OF  SYPHILIS 

1909,  to  be  tested  clinically.  The  extensive 
experiments  on  animals  of  his  collaborator 
Hata  had  already  proved  its  extraordinary 
efficacy  in  relapsing  fever  of  mice  and  rats 
and  in  syphilis  of  rabbits. 

The  Ehrlich-Hata  preparation,  ''606/'  as 
it  is  now  briefly  called,  has  been  produced 
by  Dr.  Bertheim,  who  has  for  years  worked 
with  Ehrlich.     Its  formula  is  as  follows : 

As  As 

/\  /\ 

I 

NHg  V  /NH2  =  Dioxydiamido- 

QTT  Qjj  arsenobenzol. 

In  Ehrlich's  opinion,  this  must  be  regarded 
as  the  genuine  destructive  agent  of  the 
arsenic  residue,  while  the  side-groupings 
cause  the  primary  anchoring  of  the  para- 
sites. 

I.  Experiments  on  Animals. 

Analogously  with  the  experimental  tests 
of  atoxyl  made  by  Uhlenhuth  and  his 
collaborators,  Ehrlich  and  his  co-worker 
Hata  studied  the  effect  of  the  new  prepara- 

45 


THE  THERAPY  OF  SYPHILIS 

tion  on  the  spirilla  of  relapsing  fever, 
spirillosis  of  fowls,  and  syphilis  of  rabbits, 
by  means  of  observations  on  animals. 
Thus,  from  a  large  series  of  chemical 
preparations,  Hata  succeeded  in  finding 
the  maximum  spirillicide  action  in  two 
substances  produced  by  Bertheim — namely, 
in  arsenophenylglycin,  discussed  on  pp.  40 
to  44,  and  in  the  one  just  mentioned, 
''  Ehrlich-Hata  '  606/  "  Mice,  infected  with 
the  spirilla  of  the  relapsing  fever,  were  cured 
by  a  single  dose,  which  contained  a  third  of 
the  dosis  maxima  tolerata.  According  to  the 
statements  of  Ehrlich,  Hata  obtained  most 
excellent  results  with  this  preparation  in 
spirillosis  of  fowls,  1-5  milligrammes  per 
kilogramme  of  the  animal's  weight  of  this 
combination  being  sufficient  to  effect  a  cure. 
When  transferred  to  man,  this  dose  would 
only  correspond  to  one  of  -^  gramme. 
When  a  dose  of  arsenobenzol  is  injected 
intramuscularly  into  fowls,  infection  only 
takes  effect  at  the  end  of  thirty  to  forty 
days,   but    after  intravenous   injection   it 

46 


THE  CHEMOTHERAPY  OF  SYPHILIS 

does  so  after  three  or  four  days.  Hata 
was  also  able  to  obtain  most  brilliant  results 
in  syphilis  of  rabbits.  The  cure  of  very 
large  chancres  could  be  effected  by  means 
of  a  single  dose.  On  the  day  following  the 
injection,  the  spirilla,  which  before  had  been 
present  in  large  quantities,  had  disappeared, 
and  this  was  followed  in  the  course  of  two 
to  three  weeks  by  complete  cure  with  a 
smooth  cicatrix.  Tomasczewski  was  also 
able  to  testify  to  a  good  effect  of  arseno- 
benzol  on  the  products  of  experimental 
syphilis  in  rabbits.  At  latest,  thirty-six 
hours  after  the  injection,  and  at  the  earliest, 
twelve  hours  after,  the  spirochaetes  had 
disappeared.  The  symptoms  began  to  re- 
trogress after  ten  to  fourteen  days. 

Neisser's  curative  results  were  less  favour- 
able with  apes  in  which  syphilis  had  been 
experimentally  induced.  Out  of  twelve 
S3rphilitic  apes,  which  had  been  treated 
intramuscularly  with  0'025  per  kilogramme 
weight,  and  intravenously  with  0'0i5  per 
kilogramme,  up  to  the  time  of  publication 

47 


THE  THERAPY  OF  SYPHILIS 

only  three  had  been  definitely  cured  ;  two 
were  probably  cured,  and  the  remaining 
seven  at  the  present  time  must  be  regarded 
as  uncured.  Two  apes  were  given  an 
intramuscular  injection  of  0*025  P^^^  kilo- 
gramme eleven  days  after  inoculation. 
Here  the  primary  affection  set  in  much 
later,  and  to  a  much  slighter  extent 
than  in  the  control  animals,  which  had 
been  inoculated  simultaneously,  but  not 
injected. 

Uhlenhuth  and  I,  in  the  observations 
we  made  on  animals  in  this  direction,  could 
not  determine  any  special  difference  be- 
tween the  effect  of  arsenobenzol,  atoxyl, 
and  atoxylate  of  mercury  respectively. 
With  the  last  preparation  especially,  the 
larger  doses  had  precisely  the  same  effect 
as  arsenobenzol  on  the  spirochaetes  of 
spirillosis  of  fowls,  and  syphilis  of  ra;bbits, 
as  well  as  on  their  clinical  manifesta- 
tion. We  were,  however,  able  to  prove 
the  prophylactic  power  of  an  injection 
of    arsenobenzol     against     infection    with 

48 


THE  CHEMOTHERAPY  OF  SYPHILIS 

spirillosis  of  fowls  during  a  period  extending 
over  twenty-five  days.  Observations  on 
animals  have  proved  the  superiority  of ' '  606 ' ' 
to  other  preparations  in  relapsing  fever. 

If  we  again  glance  at  the  path  which  led 
Ehrlich  and  Hata  to  the  discovery  of  this 
new  syphilitic  drug,  we  see  that  the  start- 
ing-point was  atoxyl,  the  spirillicide  and 
specific  anti-syphilitic  action  of  which  had 
been  experimentally  proved  by  Uhlenhuth. 
There  can,  therefore,  be  no  doubt  that  the 
experimental  foundation  of  the  modern 
arsenic  therapy  of  spirilloses  was  laid  by 
Uhlenhuth  and  his  co-workers.  Uhlenhuth 
himself,  when  the  toxic  secondary  effects 
of  atoxyl  became  known,  was  one  of  the 
first  to  issue  a  warning  against  its  general 
employment  in  the  treatment  of  syphilis. 
In  the  firm  conviction,  however,  that  the 
organic  arsenic  compounds  were  called  upon 
to  play  a  great  part  in  the  therapy  of 
syphilis,  he,  as  well  as  Ehrlich,  endeavoured 
to  discover  new,  less  toxic,  modifications 
of  atoxyl. 

49  o 


THE  THERAPY  OF  SYPHILIS 

The  practitioner  who  wishes  to  success- 
fully employ  the  new  remedy  ''  606  "  must 
be  accurately  instructed  as  to  its  action 
and  secondary  effects,  mode  of  application 
and  height  of  dosage.  In  the  following 
pages,  therefore,  I  shall  attempt  to  sum- 
marise the  most  important  points  from  the 
literature  on  the  subject,  which  is  already 
considerable. 

2.  Suspension   of  Solutions  which  are 
Prepared  Ready  for  Use. 

The  preparation  ''Ehrlich-Hata  '606'*' 
is  a  sulphur-yellow  powder,  hermetically 
sealed  in  a  vacuum  tube  in  correct  doses. ^ 
It  dissolves  in  hot  water  as  double  hydro- 
chloride salt,  but  Ehrlich  states,  and  the 
experience  of  Alt,  Schreiber,  and  Hoppe 
show,  that  it  should  not  be  injected  in  this 
condition,  as  it  is  liable  to  become  toxic. 
By  the  addition  of  solution  of  caustic  soda, 

^  According  to  the  most  recent  communications,  it 
has  been  placed  on  the  market  under  the  name 
"  Salvarsan,"  in  doses  of  0-6  gramme  in  hermetic- 
ally sealed  glass  tubes. 

50 


THE  CHEMOTHERAPY  OF  SYPHILIS 

it  can  be  transposed  into  mono-  or  di-sodium 
compound  and  dissolved.  This  solution, 
however,  is  not  very  stable,  and  must 
always  be  freshly  prepared. 

Now,  during  the  time  required  for  testing 
this  preparation  clinically,  the  production 
of  solutions  which  are  ready  for  use  has 
undergone  the  most  varied  changes  and 
modifications.  As  no  definite  decision  has 
yet  been  arrived  at  as  to  their  relative 
value,  I  \\dll,  as  far  as  possible,  give  all  the 
methods  known  up  to  the  present  time. 

[a)    ALKALINE   SOLUTIONS. 

I.  Iversen's  Method. — Iversen  first  in- 
jected a  0*5  to  2  per  cent,  aqueous  solution 
of  the  preparation  ''  606 "  under  the 
shoulder-blade  or  intramuscularly.  He 
gave  the  following  prescription  for  intra- 
venous injection  : 

*'  For  this  purpose  I  dissolve  the  sub- 
stance as  for  intramuscular  application,  in 
about  15  c.c.  of  aq.  dest.,  add  normal 
solution   of   caustic   soda,   drop   by   drop, 


THE  THERAPY  OF  SYPHILIS 

until  the  sediment  is  dissolved,  then  neu- 
tralise the  excess  of  caustic  soda  solution, 
drop  by  drop,  with  i  per  cent,  acetic 
acid  (about  2  c.c.  of  i  per  cent,  solu- 
tion to  0-3  arsenobenzol),  pour  this  to 
half  a  litre  of  physiological  salt  solution 
heated  to  40° ;  shake  the  bottle  (infusion 
apparatus)  moderately,  and  inject  by  means 
of  a  hollow  needle  direct  into  the  cubital 
vein/' 

2.  Alt's  Method. — The  method  origin- 
ally employed  by  A|lt  for  the  suspension  of 
solutions  ready  for  intramuscular  injections 
of  arsenobenzol  is  the  following  : 

*'  A  single  dose,  0*3  and  about  10  c.c. 

sterile  water,  is  poured  into  a  low  measuring 

glass  of  about  50  c.c.  content  and  shaken. 

Sterile  N  solution  of  caustic  soda  is  added, 

until  only  a  slight  residue  of  the  substance 

remains  undissolved ;  for  this  2*0  to  2*3  c.c. 
N   solution  of   caustic   soda  is  necessary. 

The  cylinder  is  now  filled  with  sterile  water 

up  to  the  stroke  20  c.c,  sometimes  after 

having  added  a  sterile  anaesthetic.      With 

52 


THE  CHEMOTHERAPY  OF  SYPHILIS 

a  syringe  containing  lo  c.c.  of  the  solution 
the  injection  is  made  deep  into  the  right  and 
left  gluteal  muscles,  while  slowly  pressing 
the  knob." 

Alt  still  adheres  to  the  plain  alkaline 
solution,  which  is  prepared  solely  by  the 
careful  addition  of  normal  solution  of 
caustic  soda.  After  exact  and  compre- 
hensive experiments  on  animals  and  man, 
it  has  been  proved  to  be  the  most  effective 
and  simultaneously  the  least  injurious.  Alt's 
recent  instructions  for  the  rapid  suspension 
of  a  good  alkaline  solution  are  as  follows  : 

'*  Put  about  thirty  glass  beads  of  medium 
size  (similar  to  those  used  for  filling  pen- 
holders) into  a  slender  graduated  glass 
cylinder  of  about  loo  c.c.  content,  with 
a  narrow  neck  and  glass  stopper.  Add 
10  c.c.  of  distilled  water,  and  then  the  sub- 
stance. Shake  energetically,  and  the  whole 
will  dissolve  quite  clearly.  To  every 
O'l  gramme  of  substance  add  about  0*5  c.c. 
of  normal  solution  of  caustic  soda,  and  then 
shake  energetically  for  about  half  a  minute. 

53 


THE  THERAPY  OF  SYPHILIS 

A  perfectly  wine-clear,  weakly  alkaline 
solution  has  now  been  obtained,  which  can 
be  further  diluted  at  will  by  the  addition 
of  distilled  water.  As  the  preparation  is 
not  always  equally  soluble,  a  slightly  greater 
or  smaller  quantity  of  solution  of  caustic 
soda  may  be  necessary,  in  order  to  obtain 
the  wine-clear  suspension.  This  can  be 
produced  in  the  shortest  time  without  any 
preliminary  preparation,  and  is  easily  steri- 
lised ;  it  has  the  further  advantage  that  only 
a  small  quantity  of  solution  of  caustic  soda 
is  required,  and  consequently  less  pain  is 
caused.'* 

3.  Wechselmann's  Method. — The  fol- 
lowing is  Wechselmann's  report  of  this  : 

''  At  first  I  dissolved  the  dose  of 
di-hydrochloride  of  diamidoarsenobenzol, 
which  was  hermetically  sealed  in  a  vacuum 
tube,  with  a  little  methyl  alcohol  or  glycol ; 
to  this  about  10  c.c.  of  distilled  water  was 
added,  then  i  to  2  c.c.  y^  normal  solu- 
tion of  caustic  soda;  finally  it  was  filled 
up  to  25  c.c.  with  water,  and  this  strong 

54 


THE  CHEMOTHERAPY  OF  SYPHILIS 

acid  solution  injected.  Later  we  added 
sufficient  y^  solution  of  caustic  soda  to 
give  a  slight  trace  of  opalescence,  when  the 
monohydrochloride  was  formed.  We  also 
employed  the  drug  dissolved  only  in  water 
or  in  a  little  fluid  as  above.  We  observed 
little  difference  herewith  regard  to  the  pain." 

4.  Ehrlich's  Method.  —  Instructions, 
which  Ehrlich  himself  gives  for  the  sus- 
pension of  clear  solutions  of  his  prepara- 
tion, run  as  follows  (according  to  Schreiber 
and  Hoppe)  : 

Solution  of  "  606  '*  1 :  100  {Intramuscular 
Injection). — ''Dissolve  0*6  gramme  of  the 
substance  in  3  c.c.  glycol  while  stirring  well 
with  a  glass  rod  ;  the  addition  of  a  few  drops 
of  water  will  assist  the  solution.  Now  add 
12  c.c.  water,  shake  and  dilute  with  10*3  c.c. 
|-NaOH  in  one  portion.  On  shaking, 
a  clear  solution  is  formed,  which  can  be 
made  up  to  60  c.c.  with  water. 

''It  is  advisable  that  this  entire  process 
should  be  carried  out  in  a  graduated 
cylinder." 

55 


THE  THERAPY  OF  SYPHILIS 

Attenuated  Solutions  {for  Intravenous  In- 
jections). — Solution  A:  o-6  gramme  of  the 
substance,  0-3  to  0*5  c.c.  methyl  alcohol, 
or  3  c.c.  glycol. 

Solution  B  :  240  or  more  c.c.  physiological 
NaOH  solution,  10-3  c.c.  §-NaOH. 

While  shaking  well,  solution  A  is  poured 
into  solution  B. 

5.  The  Method  of  Schreiber  and 
HoppE. — ''  A  single  dose  0*6  to  0*7  gramme 
and  0*5  methyl  alcohol  are  placed  in  a 
mixing  cylinder  of  150  c.c.  content.  As 
soon  as  the  substance  is  moistened,  about 
10  c.c.  of  sterile  water  is  added  and  thor- 
oughly shaken.  Then  add  sufficient  sterile 
y  — NaOH  solution  to  almost  entirely  dis- 
solve the  substance,  so  that  after  prolonged 
vigorous  shaking  only  the  slightest  residue 
remains  undissolved  ;  for  this  about  3^  to 
4  c.c.  of  y  — NaOH  solution  is  required. 
Fill  up  to  60  c.c,  and  of  this  solution  inject 
30  c.c.  through  a  fine  cannula,  under  the 
most  regular  pressure  possible,  into  the  right 
gluteal  muscle,  and  30  c.c.  into  the  left/' 

§6 


THE  CHEMOTHERAPY  OF  SYPHILIS 

For  intravenous  injection,  the  authors 
first  of  all  used  this  solution  without 
diluting  it,  but  later  they  cautioned  opera- 
tors against  the  employment  of  a  concen- 
trated solution.  The  exact  description  of 
their  suspension  for  intravenous  injection 
is  as  follows  : 

''  Into  a  graduated  measuring  cylinder  of 
250  c.c.  capacity  (with  a  glass  stopper  and 
narrow  neck)  put  about  10  to  20  c.c.  of 
sterile  water.  Then  add  the  substance  (0-3 
gramme  for  women  and  0*4  for  men),  and 
shake  thoroughly  until  a  clear  solution  is 
obtained.  The  addition  of  methyl  alcohol  is 
now  no  longer  necessary,  as  the  preparation 
in  this  present  form  (''  Hyperideal  606  ") 
dissolves  easily  in  water.  This  solution  is 
brought  up  to  100  c.c.  with  sterile  water  or 
physiological  common  salt  solution.  Then 
per  O'l  of  the  substance,  add  about  07  c.c. 
of  normal  NaOH  solution,  and  shake  well 
until  the  existing  residue  is  thoroughly  dis- 
solved. If  after  a  good  shaking  the  solu- 
tion is  stiU  opaque,  a  few  drops  of  normal 

57 


THE  THERAPY  OF  SYPHILIS 

NaOH  are  carefully  added  until  the  solu- 
tion is  perfectly  clear,  and  then  this  is 
filled  up  to  200  c.c.  (of  course,  instead  of 
200  ex.,  it  is  possible  to  select  either 
150  c.c.  or  250  c.c).  For  solution  as  well  as 
for  fining  up,  it  is  best  to  use  warm  water." 

{b)    NEUTRAL   EMULSIONS. 

I.  Method  of  Leonor  Michaelis. — ''  A 
wide  measuring  cylinder  of  50  c.c.  capacity 
is  filled  with  25  c.c.  of  water,  which  has  been 
boiled  a  short  time  before,  and  is  still  quite 
hot.  Then  add  0*6  gramme  of  the  sub- 
stance, and  dissolve  by  rubbing  and  stirring 
backwards  and  forwards  with  a  glass  rod. 
If  the  whole  substance  has  been  dissolved 
without  leaving  any  residue,  then  6  c.c.  of 
normal  (not  /^)  NaOH  is  added,  and  it 
is  stirred  until  the  precipitation  which 
has  resulted  is  entirely  dissolved.  Then 
3  drops  of  a  J  per  cent,  alcoholic  solution 
of  phenolphthalein  are  added,  and  normal 
acetic  acid,  while  stirring  all  the  time,  until 
the    reaction    is    neutral — i.e.,    until    the 

58 


THE  CHEMOTHERAPY  OF  SYPHILIS 

phenolphthalem  has  lost  its  colour.  The 
neutral  suspension  is  now  formed,  the 
appearance  of  which  is  bright  yellow. 
In  order  to  definitely  prevent  the  rise  of  an 
alkaline  reaction,  normal  NaOH  is  again 
added,  drop  by  drop,  until  the  phenol- 
phthalein  appears  to  be  tinged  very  slightly 
red.  This  fluid  is  poured  off  into  a  flat 
sterile  shell,  and  injected  subcutaneously 
into  the  back." 

Later,  Michaelis  deviated  somewhat  from 
the  above-described  method,  in  that  he 
moistened  the  solid  preparation  with  i  c.c. 
absolute  ethyl  alcohol  in  the  measuring 
cylinder,  and  pricked  through  with  the  glass 
rod  until  the  preparation  was  thoroughly 
wetted  everywhere  with  the  alcohol.  The 
hot  water  was  then  poured  on,  and  solu- 
tion rapidly  obtained  by  simply  stirring 
with  the  glass  rod. 

2.  Method  of  Wechselmann  and 
Lange. — Almost  simultaneously  with  L. 
Michaelis,  Wechselmann  devised  the  follow- 
ing methods  of  suspension  : 

59 


THE  THERAPY  OF  SYPHLHS 

{a)  ''  606  "  is  dissolved  as  before,  a  few 
drops  of  phenolphthalein  solution,  as  an 
indicator,  and  xtt  NaOH  carefully  added, 
until  a  fine  yellow  powder  is  again  preci- 
pitated. This  weakly  acid  or  neutral 
suspension  of  25  to  30  ex.  is  injected 
intramuscularly  or  subcutaneously  into  the 
gluteal  region. 

(b)  After  rubbing  "  606  "  in  a  mortar,  it 
is  dissolved  in  i  to  2  c.c.  of  commercial 
NaOH  solution.  By  adding  glacial  acetic 
acid  drop  by  drop,  a  fine  yellow  sediment 
is  precipitated,  which  can  be  sterilely  sus- 
pended with  I  to  2  c.c.  of  distilled  water, 
and  then  neutralised  by  the  addition  of 
Y^  NaOH  or  i  per  cent,  acetic  acid  most 
accurately  with  litmus-paper.  The  absence 
of  pain  depends  upon  the  accuracy.  The 
suspension  is  drawn  into  the  syringe,  and 
injected  slowly  subcutar^eously  under  the 
shoulder-blade,  at  a  place  which  has  been 
previously  disinfected. 

3.  Spiethoff's  Method. — By  modify- 
ing the  instructions  laid  down  by  Michaelis 

60 


THE  CHEMOTHERAPY  OF  SYPHILIS 

for  the  preparation  of  an  emulsion,  it  is 
possible,  according  to  Spiethoff,  to  reduce 
the  amount  of  the  injection  when  using 
0'6  gramme  arsenobenzol  from  9  to  10  c.c. 
0'6  gramme  of  the  substance  is  placed  in 
a  large  centrifugal  glass.  To  this  is  added 
a  few  c.c.  of  hot  sterile  physiological  saline 
solution.  It  is  shaken  thoroughly  and 
broken  up  with  the  glass  pestle,  with 
the  addition  of  further  hot  physiological 
saline  solution.  For  the  preparation  of  a 
complete  suspension,  8  c.c.  of  saline  solution 
is  adequate.  Then  add  2  drops  of  phenol- 
phthalein  and  about  3  drops  of  concen- 
trated NaOH  solution.  A  few  rough 
reddish  flakes  will  form,  which  on  stirring 
become  more  and  more  numerous  and 
finer,  until  finally  a  pulpy  mass  appears, 
which  becomes  a  fine  emulsion  with  further 
stirring  and  occasionally  warming  the  glass 
in  hot  water.  Add  a  few  drops  of  concen- 
trated NaOH  until  a  light  reddish  colour 
appears,  when  a  few  drops  of  strong  acetic 
acid  solution  must  be  added,  till  the  red 

61 


THE  THERAPY  OF  SYPHILIS 

colour  again  disappears.  The  excess  of 
alkali  is  again  removed  at  the  bedside 
immediately  before  the  injection  itself,  by 
means  of  a  few  drops  of  normal  NaOH. 
Any  residue  left  in  the  glass  is  washed 
out  by  I  ex.  of  sterile  distilled  water. 
In  this  way,  one  can  reduce  the  volume 
required  for  the  injection  of  0-6  gramme  to 
about  9  or  lo  c.c,  which  has  the  result  of 
diminishing  the  pain." 

4.  Method  of  Blaschko. — According  to 
Blaschko,  one  should  only  add  just  suffi- 
cient soda  to  again  precipitate  the  base  out 
of  the  salt.  ''  The  amount  can  be  deter- 
mined just  as  well  by  calculation  as  by 
rubbing.  For  0*5  gramme  of  the  salt  it 
requires  0*45  gramme  =  0*36  of  a  20  per 
cent.  NaOH;  for  0*45  gramme  of  the 
preparation,  0*41  gramme  =  0*33  c.c.  NaOH; 
for  o*o6  gramme  of  the  precipitation,  0*55 
gramme  =0*45  solution  of  caustic  soda.  If 
the  soda  is  added  carefully,  and  a  little 
sterile  water,  it  is  possible  to  at  once  pro- 
duce a  neutral  suspension,  or  at  most  one 

62 


THE  CHEMOTHERAPY  OF  SYPHILIS 

that  requires  one  or  two  drops  of  weak 
acetic  acid  or,  better  still,  hydrochloric 
acid.  If  the  emulsion  is  then  filled  up 
to  8  or  9  ex.,  we  have  a  physiological  com- 
mon salt  solution  of  0*82  to  075  per  cent, 
which  contains  a  suspension  of  the  base. 
It  is  sufficient,  however,  if  it  is  filled  up  to 
5  ex.,  for  a  saline  solution  of  1-3  per  cent, 
is  not  so  hypertonic  that  it  is  painful  in 
any  way." 

5.  Method  of  H.  Citron  and  the 
Author. — Starting  from  the  fact  that  all 
manipulations  for  the  suspension  of  ready- 
prepared  solutions  of  arsenobenzol  already 
described,  are  associated  with  certain  details 
which  may  appear  undesirable  for  the  busy 
medical  man,  and  more  especially  because 
the  possibility  of  chemical  changes  in  the 
very  subtle  preparation  may  render  sterile 
work  difficult,  we  have  devised  the  follow- 
method  : 

''  The  necessary  amount  of  Hat  a  powder 
for  injection  is  shaken  into  a  sterile  Record 
sjnringe  of  15  c.c.  capacity,  which  is  closed 

63 


THE  THERAPY  OF  SYPHILIS 

with  a  cone  at  one  end  of  the  cannula,  and 
moistened  with  a  few  drops  of  alcohol. 
The  stopper  has  been  previously  removed. 
The  syringe  is  filled  up  to  mark  5  with  hot 
distilled  water,  the  stopper  readjusted, 
the  ligature  ring  put  on,  and  thoroughly 
shaken.  A  clear  golden- yellow  solution 
results.  The  stopper  is  now  taken  out 
again,  and  40  drops  of  a  10  per  cent,  sus- 
pension of  calcium  carbonate  in  physio- 
logical NaCl  solution  added  slowly  while 
shaking  continuously.  By  removing  the 
cone,  a  little  carbonic  acid  is  allowed  to 
escape  from  time  to  time.  A  creamy, 
extremely  fine  emulsion  is  formed,  some- 
what of  the  appearance  and  consistency  of 
egg  brandy.  The  addition  of  40  drops  of 
the  10  per  cent,  calcium  carbonate  sus- 
pension is  found  from  experience  to  be  suffi- 
cient for  the  complete  precipitation  of  the 
base.  As  we  have  been  able  to  convince 
ourselves  by  centrifugalisation,  the  fluid 
decanted  is  entirely  without  colour.  In 
contradistinction   to   the   old   methods   of 

64 


THE  CHEMOTHERAPY  OF  SYPHILIS 

suspension,  a  small  excess  of  the  precipi- 
tate is  without  importance.  The  resulting 
amount  injected  consists  of  about  5  to 
6*5  ex.,  but  we  have  no  doubt  that  one 
could  make  smaller  quantities  suffice.  After 
the  precipitation  is  finished,  the  stopper 
is  screwed  on,  and  a  cannula  appended, 
which  is  not  too  fine.  We  select  the  upper 
external  quadrant  of  the  gluteal  region  ex- 
clusively as  the  seat  of  injection." 

The  10  per  cent,  calcium  carbonate  sus- 
pension is  sterilised  by  placing  it  in  a  drop- 
glass,  which  is  closed  by  a  wadding  plug, 
and  sterilised  in  the  autoclave. 

{c)  kromayer's  paraffin  emulsion. 

Kromayer  employs  the  preparation 
*'  606  "  in  the  form  in  which  it  is  sent — 
viz.,  as  a  dichlorate — by  making  an  emul- 
sion with  paraffin,  analogous  to  a  mer- 
curial paraffin  emulsion,  which  he  prepares 
as  follows  : 

''  A  certain  amount  of  Ehrlich's  '  606  ' 
— for  example,  3  grammes — is  mixed  with 

65  E 


THE  THERAPY  OF  SYPHILIS 

a  little  liquid  paraffin  in  a  sterile  mortar, 
and  is  carefully  rubbed  very  fine,  while 
more  paraffin  is  gradually  added.  It  is 
put  in  a  sterile  bottle,  of  50  c.c.  capacity, 
with  a  glass  stopper,  and  is  filled  up  to 
30  c.c,  so  that  each  c.c.  of  the  emulsion 
contains  o-i  gramme  of  Ehrlich's  ''  606."  It 
must  be  shaken  before  using  until  all  sedi- 
ment has  disappeared  and  be  protected  from 
light.  On  account  of  the  fear  of  the  cannulas 
becoming  blocked,  they  should  be  selected 
somewhat  stronger  than  those  used  for 
Hg  salicylic  injections,  and  it  is  best  to 
keep  them  in  Petri  saucers,  covered  with 
liquid  paraffin.  In  this  case,  it  is  no  more 
necessary  to  sterilise  the  cannula  each  time 
before  using  than  it  is  in  Hg  injections. 
The  injections  with  ''606''  are  made  exactly 
in  the  same  way  as  the  former,  and  ambulant 
patients  can  also  be  treated.'' 

These  are  the  principal  methods  which 
have  been  proposed  and  clinically  tested 
by  many  authors  up  to  the  present  for 
the  purpose  of  making  the  new  Ehrlich 

66 


THE  CHEMOTHERAPY  OF  SYPHILIS 

preparation  ''  606 "  ready  for  use.  Still 
further  small  alterations  of  these  methods 
have  been  proposed  by  various  authors. 
Thus,  Loeb  adds  i  to  3  c.c.  i  per  cent, 
acetic  acid  to  the  alkaline  solution^  as,  in 
his  experience,  the  pain  of  the  alkaline 
solution  is  thus  considerably  diminished. 
The  fact  that  this  solution  is  less  painful  is 
obviously  due  to  the  solution  of  caustic 
soda  being  partially  neutralised,  which  is 
evidenced  by  the  gelatinous-nuclear  pre- 
cipitation. Saalfeld,  Frankel,  and  Grouven 
only  add  i  to  i|  c.c.  of  ^u  NaOH  solu- 
tion to  the  hydrochloric  solution,  which 
certainly  does  not  intrinsically  influence 
the  acid  reaction.  Junkermann  does  not 
employ  normal  NaOH  solution  for  the 
purpose  of  alkalisation,  but,  instead,  the 
strong  official  15  per  cent,  solution  of 
caustic  soda. 

Passini  prepares  a  neutral  or  very  weakly 
acid  emulsion  by  means  of  NaOH  and 
glacial  vinegar  in  the  usual  way,  and  then 
rubs  this  mass  carefully  with  a  mixture  of 

67 


THE  THERAPY  OF  SYPHILIS 

adeps  lanae  anhydricum  and  vaseline  oil 
in  equal  parts. 

Nearly  all  these  methods  for  the  prepara- 
tion of  ready-tO"Use  solutions  have  been 
found  to  be  equally  good  in  animal  experi- 
ment and  by  the  sick-bed.  According  to 
Hata's  observations  on  animals^  the  pre- 
paration is  quickly  secreted  when  injected 
intravenously,  whereas,  when  administered 
subcutaneously  and  intramuscularly,  it  re- 
mains deposited  in  the  body  a  long  time, 
and  develops  a  prolonged  action.  With 
regard  to  the  rapidity  of  the  disappearance 
of  the  spirochaetes  from  the  syphilitic 
diseased  tissue,  Spiethoff  was  unable  to 
discern  any  difference  between  the  effect 
of  the  solution  and  that  of  the  emul- 
sion. Nevertheless,  from  the  researches  of 
various  authors  (A.  Neisser  and  others), 
the  action  of  neutral  emulsions  appears 
to  be  slower,  but  more  persistent.  Alt, 
Schreiber,  Hoppe,  and  others,  attributed  a 
more  rapid,  but  at  the  same  time  less 
lasting,  effect  to  the  intravenous  incorpora- 

68 


THE  CHEMOTHERAPY  OF  SYPHILIS 

tion  of  the  preparation.  For  this  reason, 
Iversen  combined  this  mode  of  appUca- 
tion  with  intramuscular  injection  —  a 
method  which  is  also  recommended  by 
Ehrlich — in  such  a  way  that  he  first  injected 
a  little  over  half  (0-4  to  0-5  gramme)  the 
dose  of  arsenobenzol  intravenously,  and 
at  the  end  of  forty-eight  hours  injected 
the  remainder  (0-3  to  0*4  gramme)  intra- 
muscularly. Wechselmann,  L.  Michaelis, 
Herxheimer,  Sieskind,  and  others,  as  a  rule 
prefer  to  make  a  subcutaneous  injection 
in  the  interscapular  region  or  between  the 
shoulder-blades,  whereas  the  majority  of 
teachers  like  an  intramuscular  injection 
deep  in  the  gluteal  region. 

In  the  experience  of  Alt,  the  incorpora- 
tion of  acid  solutions,  as  already  men- 
tioned, is  apparently  not  innocuous,  and 
even  in  small  doses  they  may  have  an  un- 
favourable effect  upon  the  heart's  action. 
Even  Ehrlich  himself,  as  well  as  Junker- 
mann  and  others,  suspects  that  the  prepara- 
tion as  dichlorohydrate  may  have  an  irri- 

69 


THE  THERAPY  OF  SYPHILIS 

tant  and  occasionally  a  toxic  action  on  the 
tissue.  This  suspicion  would  also  apply  to 
Kromayer's  paraffin  emulsion,  in  which, 
further,  the  bad  absorptive  capacity  must 
be  taken  into  consideration.  If  these  sus- 
picions, however,  are  got  rid  of,  as  Kro- 
mayer  has  reported^  after  extensive  clinical 
application  and  observation,  then  the  par- 
affin or  vaseline  oil  emulsion  he  recom- 
mends may  possibly  be  used  for  injection 
and  for  the  practical  employment  of  the 
preparation.  Meirowsky,  however,  could 
not  confirm  Kromayer's  assertions  that 
this  method  of  injection  only  caused  slight 
pain.  Further,  he  fears  the  possibility  of 
the  great  quantity  of  parafhn  injected 
favouring  embolism,  a  circumstance  which 
he  verified  in  an  observation  of  his  own. 
Similarly,  the  method  which  Citron  and  I 
worked  out  should  be  recommended  for 
medical  practice,  as  the  ready-prepared 
solution,  which  guarantees  the  smallest 
imaginable  chemical  changes,  is  absolutely 
sterile  and  perfectly  neutral,   and  conse- 

70 


THE  CHEMOTHERAPY  OF  SYPHILIS 

quently  fairly  painless  in  itself.  The 
momentary  action  of  this  emulsion  is 
apparently  like  that  of  others,  but  whether 
the  conditions  of  absorption  are  also  the 
same  can  only  be  determined  after  a  larger 
number  of  cases  have  been  treated  with  it. 
Still,  one  may  assume  that  these  would 
certainly  not  be  more  unfavourable  than 
with  Kromayer's  paraffin  emulsion,  de- 
scribed above. 
As  regards  the 

3.  Technique  of  Injection, 

the  following  points  are  worthy  of  observa- 
tion, from  experience  gained  up  to  the 
present  : 

{a)    INTRAMUSCULAR  INJECTION. 

This  is  made  in  the  muscles  of  the 
gluteal  region,  as  in  the  intramuscular 
application  of  mercurial  preparations.  It 
is  best  for  the  patient  to  lie  on  his  abdomen 
when  on  the  operating- table.  The  gluteal 
region    is    disinfected    in    the    usual    way 

71 


THE  THERAPY  OF  SYPHILIS 

(according  to  Fiirbringer,  with  tincture  of 
iodine  or  iodine  benzine),  and  the  puncture 
is  made  in  the  upper  external  quadrant. 
In  order  to  remain  as  far  as  possible  from 
the  sciatic  nerve,  and  so  avoid  more  in- 
tense pain,  Junkermann  advises  that  the 
injection  should  be  made  at  the  height  of 
the  connecting  line  of  the  spinae  iliacae 
anteriores  superiores,  and  the  cannula  in- 
serted slowly  into  the  gluteal  region  in  a 
sagittal  direction,  and  as  far  laterally  as 
possible.  This  is  done  in  order  to  avoid 
piercing  the  larger  vessels  of  the  gluteal 
region.  When  employing  solutions  of  the 
preparation,  the  injection  can  follow  at 
once  with  the  usual  cannula.  Air  bubbles 
must  obviously  be  prevented.  When  in- 
jecting emulsions,  it  is  better  to  employ 
somewhat  larger  needles,  and,  as  in  insoluble 
mercurial  preparations,  remove  them  from 
the  syringe  before  the  inj  ection,  in  order  to 
convince  oneself  that  no  vessel  has  been 
pierced  (Lesser's  handle  should  be  used). 
The  injection  itself  is  always  made  extremely 

72 


THE  CHEMOTHERAPY  OF  SYPHILIS 

slowly,  in  order  to  avoid  tearing  the  tissue 
as  much  as  possible  (Kromayer) .  If  neutral 
emulsions  are  injected,  then  the  relatively 
small  amount  required  can  be  syringed  into 
one  side  of  the  gluteal  region.  It  is  best 
to  select  the  side  on  which  the  patient  as 
a  rule  does  not  sleep  (Spiethoff  and  others) . 
It  is  advisable  that  the  patient  should 
remain  lying  on  his  abdomen  for  a  little 
time  longer.  After  the  seat  of  injection 
has  been  fastened  with  a  sterile  plug, 
covered  with  a  wide  piece  of  sticking- 
plaster,  the  region  should  be  vigorously 
massaged  for  about  half  an  hour.  Vibra- 
tory massage  may  also  be  applied  as  after 
a  mercurial  injection. 

{b)    SUBCUTANEOUS   INJECTION. 

This  is  recommended  chiefly  by  Wech- 
selmann  and  Lange,  L.  Michaelis  and 
Kromayer.  The  patient,  according  to 
L.  Michaelis,  is  placed  in  a  completely 
perpendicular  position,  and  the  cannula  in- 
serted in  the  region  between  the  shoulder- 

73 


THE  THERAPY  OF  SYPHILIS 

blades.  *'  After  emptying  the  syringe,  the 
dispersion  of  the  injected  mass  follows, 
which  is  the  most  important  part  of  the 
entire  procedure.  The  patient  is  seated 
transversely  on  the  bed  in  an  upright 
position,  and  then,  by  means  of  careful 
massage,  the  ball  of  fluid  is  spread  over 
the  greatest  possible  surface,  so  that  no 
further  protuberances  are  visible.  Then  a 
moist  dressing  is  applied  to  the  back,  and 
the  patient  put  to  bed.''  Michaelis  now 
makes  the  injections  somewhat  deeper  into 
the  dorsal  muscles  ;  he  no  longer  injects 
quite  at  the  back,  but  instead  laterally 
and  under  the  thorax. 

Wechselmann  and  his  collaborators 
(Lange  and  Sieskind)  make  the  subcutaneous 
injection  in  the  right  interscapular  region. 

Blaschko  injects  into  the  subcutaneous 
tissue  of  the  nates,  and  considers  that  in 
this  way,  with  hardly  perceptible  infiltra- 
tion, all  functional  disturbances  are  avoided. 
Moreover,  in  order  that  the  conditions  of 
absorption   may  be   more  favourable,   he 

74 


THE  CHEMOTHERAPY  OF  SYPHILIS 

spreads    the    dose    injected    over    various 
places  in  smaller  quantities. 

Larger  ''  Record ''  syringes  are  most 
suitable  for  both  intravenous  and  intra- 
muscular injections. 

(c)    INTRAVENOUS   INJECTION. 

An  accurate  description  of  the  intra- 
venous injection  is  given  by  E.  Schreiber, 
which  I  will  quote  here  in  his  own  words  : 

''  The  solution  (see  p.  57)  is  then  put  into 
a  sterile  measuring  glass,  from  which  it 
can  be  easily  sucked  up  with  the  syringe. 

''  The  syringe  we  now  employ  is  a  simple 
Liier  one.  The  cannula  is  bayonet-shaped, 
bent,  and  has  a  lateral  attachment-piece 
with  a  three-way  stopcock,  so  that  not  only 
can  the  fluid  be  drawn  up,  but  after  the 
tap  is  turned  it  can  be  injected  into  the 
vein.  Further,  the  cannula  has  also  a 
small  plate  bent  at  right  angles  at  the  first 
joint,  for  the  purpose  of  fixing  the  syringe 
better.  It  is  now  made  to  screw  off,  so 
that  it  can  be  easily  changed. 

75 


THE  THERAPY  OF  SYPHILIS 

'*  It  is  very  important  that  the  cannula 
should  rest  properly  in  the  vein,  and  that  on 
puncturing  no  further  injury  should  be 
done,  which  may  easily  happen  with  the 
cannula  if  the  syringe  is  too  long  ;  there- 
fore, I  only  have  the  syringe  obtusely 
bevelled.  In  order  to  be  absolutely  cer- 
tain, we  use  a  short  handle,  which  I  can 
thoroughly  recommend,  especially  to  those 
who  are  making  the  injection  for  the  first 
time. 

''  We  first  fill  the  syringe  with  physio- 
logical saline  solution  ;  then,  with  the  tap 
open,  pierce  into  the  vein,  and  while  the 
ligature  is  still  in  position,  make  the 
injection,  only  syringing  in  the  saline 
solution  after  blood  has  poured  in  dis- 
tinctly. Now,  if  the  cannula  does  not  rest 
completely  in  the  vein,  or  this  has  been 
injured  in  any  way  by  the  puncture,  in- 
filtration will  at  once  resujlt  on  injecting 
the  saline  solution.  If  this  occurs,  we 
withdraw  the  cannula  from  the  vein  and 
try  to  find  another  better  position.  In  every 

76 


THE  CHEMOTHERAPY  OF  SYPHILIS 

case  care  must  be  taken  to  prevent  any 
of  the  solution  getting  under  the  skin  in 
the  subsequent  injection  ^  because  this 
causes  unpleasant  infiltrations.  In  some 
instances  these  are  very  painful  and  per- 
sist for  weekSj  although  later^  without 
exception  J  they  recover  well.  Consequently, 
we,  as  a  rule,  select  a  vein  which  lies  out- 
side the  elbow-joint,  so  that,  in  the  event 
of  such  infiltrations,  movement  is  not  in- 
terfered with.  Similarly,  when  the  whole 
of  the  solution  has  been  injected,  we  again 
syringe  out  the  vein  with  saline  solution, 
in  order  to  avoid  any  irritant  action  upon 
the  lower  parts  of  the  vein.  If,  during  the 
injection  of  the  solution,  the  cannula  should 
be  withdrawn  from  the  vein,  or  have 
injured  it,  then  a  protuberance  will  at  once 
appear  on  injecting,  and  the  patient  will 
at  the  same  moment  complain  of  a  burn- 
ing feeling.  The  syringe  should  be  at  once 
withdrawn,  the  ligature  replaced,  and  a 
reasonable  amount  of  bleeding  allowed, 
because  we  have  found  that  this  is  the  best 

n 


THE  THERAPY  OF  SYPHILIS 

way  to  avoid  infiltration.  If  technically 
the  injection  has  been  a  complete  success, 
the  patient  will  have  no  pain  apart  from 
the  small  punctm*e/' 

Besides  the  intravenous  injections  with  a 
cannula  provided  with  a  tap  and  syringe, 
described  by  Schreiber,  an  infusion  into 
the  vein  through  rubber  tubing  and  a 
funnel  (Weintraub)  has  been  practised 
successfully.  Assmy  has  brought  out  a 
small  set  of  instruments  for  this  purpose, 
with  which  it  is  possible  to  give  an  intra- 
venous injection  without  any  assistance ; 
this  could  hardly  be  done  with  the 
Schreiber  method.  Another  advantage 
of  the  Assmy  set  of  instruments  over 
those  of  Schreiber  is  their  cheapness  and 
greater  durability.  On  a  stand  about 
I  millimetre  high  (volumetric  stand)  two 
funnels  are  fastened  for  the  reception  of 
the  ''  606 ''  and  saline  solutions  respectively ; 
two  tubes  start  from  them.  These  are 
united  by  a  two-way  stopcock  (Posner's 
catheter  tap)  ;   on  its  attachment  a  thin 

78 


THE  CHEMOTHERAPY  OF  SYPHILIS 

rubber  tubing,  about  12  c.c.  long,  is  fixed, 
which  has  a  metal  cone  at  the  end  for  the 
reception  of  the  cannula.  The  latter  cor- 
responds in  form  to  the  Strauss  cannula, 
as  it  is  generally  applied  for  the  removal 
of  blood  for  the  Wassermann  reaction, 
only,  naturally,  it  is  thinner,  shorter, 
and  its  end  is  bevelled  off  obtusely  in  the 
same  way  as  the  Schreiber  stopcock  cannula. 
The  arrangement  of  the  rubber  tubing 
between  the  cannula  and  stopcock  makes 
it  possible  to  carry  out  all  possible  manipu- 
lations with  the  latter  without  the  cannula, 
which  is  resting  in  the  vein,  participating 
in  the  movements  thus  caused.  This  is  a 
great  advantage,  as  with  the  Schreiber 
method  the  danger  of  injuring  the  walls 
of  a  vein  naturally  persists  during  the 
entire  interference.  In  consequence  of  the 
long  lever  which  is  formed  by  the  syringe 
and  the  stopcock  cannula,  even  the  slightest 
movements,  such  as  cannot  possibly  be 
avoided  in  the  individual  phases  of  the 
injection,    are   unpleasantly    perceived    in 

79 


THE  THERAPY  OF  SYPHILIS 

an  exaggerated  form  on  the  syringe 
cannula. 

Assmy,  who  has  carried  out  numerous 
intravenous  manipulations  in  both  ways, 
states  that  the  infusion  method  is  incom- 
parably easier,  and  demands  less  expertness 
than  the  Schreiber  injection  technique. 

Whereas  Ehrlich,  even  in  his  book^ 
(p.  152),  recommended  the  intramuscular 
injection,  and  attributed  a  more  persistent 
and  intense  action  to  it,  in  a  circular  letter 
of  October  25,  1910,  he  advises  that,  in 
the  further  treatment  of  syphilis  with 
his  preparation,  the  intravenous  injection 
should  be  employed  whenever  possible. 

From  the  standpoint  of  guaranteeing  a 
permanent  result,  Ehrlich  now  considers 
that  the  following  are  most  effective  : 

1.  The  intravenous  injection  of  alkaline 
highly  attenuated  solution. 

2.  The  intramuscular  injection  of  alka- 
line solution. 

^  ''  The  Experimental  Chemotherapy  of  Spirilloses  " 
(Rebman  Limited,  1911). 

80 


THE  CHEMOTHERAPY  OF  SYPHILIS 

3.  The  strongly  irritant  acid  solutions 
(mono-dichlorhydrate) . 

4.  Finally,  the  so-called  neutral  emul- 
sions (intramuscularly  and  subcutaneously) . 

4.  Direct  Local  Secondary  Effects  of 
THE  Injection. 

Whereas  with  correct  technique  no  local 
secondary  effects  are  attached  to  the  intra- 
venous injection,  various  local  disturbances 
are  evident  with  the  intramuscular  and 
subcutaneous  application  of  the  Ehrlich 
preparation.  These  are  induced  partly  by 
the  kind  of  solution,  partly  as  the  result  of 
pressure  of  the  greater  or  smaller  quantity 
of  the  substance  injected. 

These  local  secondary  effects  are  most 
intense  and  unpleasant  with  the  injection 
of  alkaline  solutions,  especially  when  larger 
quantities  of  fluid  are  employed,  as  was  done 
almost  always  at  the  beginning. 

These  secondary  effects  appear  first  of 
all  as  pain  in  the  buttocks.     When  alkaline 

81  F 


THE  THERAPY  OF  SYPHILIS 

solutions  are  employed,  the  pain  generally 
sets  in  during  the  injection,  and  increases 
in  intensity  within  the  following  hours. 
Consequently,  it  is  advised  that  the  in- 
jection should  be  made  in  the  morning,  so 
as  to  interfere  as  little  as  possible  with  the 
patient's  night's  rest. 

As  already  mentioned,  the  pain  increases 
the  following  day.  It  is  of  a  boring 
character,  something  like  toothache,  and, 
further,  there  is  generally  a  feeling  of 
pressure  in  the  gluteal  region,  which  mean- 
while has  become  as  hard  as  board,  in- 
filtrated, and  diffusely  swollen.  This  pain 
affects  the  patients  most  when  walking, 
sitting,  and  lying  down.  Very  often  the 
tension  makes  it  almost  impossible  to  move 
the  thigh.  Moreover,  the  pain  may  be 
localised  in  the  region  of  the  os  coccyx 
(Spatz).  With  the  intramuscular  injection 
of  neutral  emulsions,  the  pain  as  a  rule 
only  begins  on  the  following  day,  attaining 
its  highest  point  on  the  second  or  third 
day,  during  which  time,  under  symptoms 

8« 


THE  CHEMOTHERAPY  OF  SYPHILIS 

of  regular  fever,  a  fairly  circumscript,  hard 
infiltration  has  been  formed,  the  size  of 
which  varies  with  the  larger  or  smaller 
amount  of  emulsion  Vv^hich  has  been  in- 
jected. The  sensation  of  pressure  here  is 
markedly  less  severe  than  with  alkaline 
solutions,  and  the  pain  is  no  longer  felt 
as  a  boring  one,  but,  instead,  as  a  dull, 
painful  pressure.  Latterly,  various  authors 
have  observed  severe  necrosis  extending  up 
to  the  bone  at  the  seat  of  puncture,  in 
intramuscular  as  wel]  as  subcutaneous  ad- 
ministration. Thus  Dreuw  in  two  cases 
observed  necrosis  of  the  gluteal  muscles, 
almost  the  size  of  a  small  fist,  and  in  another 
case  there  were  two  necroses  the  size  of 
hazel  nuts  in  the  back.  Bayet  saw  eight 
severe  gangrenous  affections  in  eight 
patients,  which  were  in  part  connected  with 
necrosis  of  the  bone  at  the  seat  of  injection. 
The  greater  percentage  of  patients  are 
supposed  to  tolerate  the  injection  excel- 
lently and  without  reaction  in  cases  of 
subcutaneous     application     (Sieskind,     L 

83 


THE  THERAPY  OF  SYPHILIS 

Michaelis,  Kromayer,  and  others).  Accord- 
ing to  Sieskind,  however,  with  the  subcu- 
taneous method  also  reaction  phenomena 
were  observed  in  about  lo  per  cent,  of 
the  cases.  The  occasional  infiltration  only 
sets  in  here  after  three  or  four  days.  It 
was  frequently  possible  to  determine  a 
fluctuation  in  the  infiltration,  which,  how- 
ever, in  Sieskind's  opinion,  owed  its 
origin  to  a  serous  fluid,  as  was  proved  by 
the  exploratory  puncture.  Out  of  275 
cases,  Sieskind  only  five  times  observed 
genuine  suppuration.  The  pus  was  sterile 
in  all  five  cases.  ''  Quite  small  necroses 
at  the  seat  of  puncture  are  not  rare,  which 
is  not  surprising  when  one  considers  the 
inflammatory  and  necrotic  effect  of  arsenic 
preparations.  The  small  necroses  healed 
by  granulation.''  Two  patients  had  ne- 
croses as  large  as  two-shilling  pieces  ex- 
tending to  the  muscle.  According  to 
Sieskind's  observations,  necrosis  always  sets 
in  if  any  of  the  preparation  has  been  left 
behind  in  the  puncture  canal. 

84 


THE  CHEMOTHERAPY  OF  SYPHILIS 

The  very  unpleasant  irritation  of  the 
sciatic  nerve  may  be  regarded  as  a  direct 
effect  of  this  infiltration,  and  this  may  make 
itself  evident  in  neuralgic  pains,  which 
extend  right  down  to  the  calf  of  the  leg. 
In  cases  in  which  there  is  a  pronounced 
inclination  to  sciatic  troubles,  or  in  which 
sciatica  exists,  an  intramuscular  injection 
should  be  avoided,  as  this  pain,  as  I  my- 
self saw  in  one  case,  is  increased  thereby, 
or  may  again  break  out. 

In  order  to  prevent — or  at  least  diminish 
— the  pain  of  injection,  which  under  some 
circumstances  may  be  very  considerable, 
not  only  with  neurasthenics,  but  also  with 
healthy,  robust  persons,  it  was  at  first 
recommended  from  various  sources  that 
an  anaesthetic  should  be  added  to  the 
injection  fluid.  Thus,  Alt  advised  the 
addition  of  an  ampulla  of  eusemin.  Wech- 
selmann  renders  the  seat  of  injection  anaes- 
thetic by  means  of  a  preliminary  injection 
of  0*02  novocain ;  others,  again,  add  cocaine, 
alypin,    or   morphia.     But    the    transitory 

S5 


THE  THERAPY  OF  SYPHILIS 

nature  of  all  these  precautions  made  them 
no  protection  against  subsequent  pain. 
Apparently  the  best  prophylactic,  as  already 
mentioned,  is  to  neutralise  the  liquid  as 
accurately  as  possible,  and  to  massage  the 
seat  of  injection  immediately  after  the 
operation.  Good  service  is  rendered  by 
permanent  bandages  moistened  with  acetic 
acid.  Fuller's  earth,  or  spirit,  as  a  pro- 
tection against  the  pain  of  pressure. 
Further,  the  usual  narcotics,  such  as 
opium,  are  best  here  as  suppositories  and 
hypnotics. 


5.  Effect  of  Arsenobenzol  on  the 
Organism  in  General. 

As  far  as  the  influence  of  the  preparation 
concerns  assimilation,  Hoppe  was  able  to 
testify  to  a  favourable  effect  on  the  lecithin 
assimilation.  With  most  patients,  a  few 
days  after  the  injection  fairly  considerable 
leucocytosis  sets  in.  A.  Neisser  also  saw 
very  pronounced  hyperleucocytosis  (up  to 

86 


THE  CHEMOTHERAPY  OF  SYPHILIS 

38,000),  the  dissonance  of  which  occurred 
slowly.  Brandle  and  Clingestein  obtained 
almost  the  same  result  (up  to  15,000), 
whereas  in  isolated  cases  Lange  only  saw 
a  slight  increase  of  leucocytes. 

Klausner  and  Bardachzi  noticed  great 
variations  in  the  number  of  red  blood- 
corpuscles  after  an  injection  of  arseno- 
benzol,  generally  during  the  first  eight  to 
twelve  hours,  accompanied  by  the  appear- 
ance of  urobilinuria ;  the  latter  again  dis- 
appeared usually  after  twenty-four  hours. 

Alt  states  that  in  intravenous  injection 
the  secretion  of  arsenic  is  almost  com- 
pleted at  the  end  of  two  days,  and  on  the 
third  day  only  traces  are  found.  ''  Within 
this  period,  one  can  detect  nearly  the  whole 
of  the  arsenic  in  the  faeces  and  urine,  apart 
from  small  quantities  which  are  lost  through 
perspiration,  the  skin,  hair,  etc.*'  In  in- 
tramuscular injections  the  secretion  of 
arsenic  lasts  at  least  twelve  to  thirteen 
days  (Treupel  and  others),  whereas  in 
intravenous   injections   it  has  already  ter- 

87 


THE  THERAPY  OF  SYPHILIS 

minated  at  the  end  of  four  days  (Hoppe). 
A  methaemoglobin  formation,  such  as  might 
be  expected  in  an  intravenous  injection, 
Heuber  says  does  not  take  place,  even  with 
the  strongest  concentration. 

W.  Fischer,  on  the  other  hand,  reports 
that,  according  to  the  researches  of  Pro- 
fessor Loeb  (Chemical  Institute  of  the 
Rudolph  Virchow  Hospital),  in  three  cases 
the  presence  of  arsenic  was  discovered  in 
the  urine,  although  in  some  of  them  only 
in  small  quantities — in  the  first  case,  eleven 
and  thirteen  weeks  after  the  subcutaneous 
dose  of  0*15  gramme;  in  the  second,  eight  and 
ten  weeks  after  ;  and  in  the  third  case,  seven 
to  eight  weeks  after  the  injection.  Fischer 
concludes  from  this  that  arsenic  may  still 
be  circulating  in  the  body  almost  three 
months  after  the  injection. 

Nearly  all  teachers  agree  that  an  in- 
jection of  arsenobenzol  has  a  very  good 
effect  on  the  patient's  general  condition, 
which  is  frequently  evidenced  first  of  all 
by   considerable   increase   in   weight.     Ac- 

88 


THE  CHEMOTHERAPY  OF  SYPHILIS 

cording  to  Wechselmann,  many  patients 
feel  ''as  if  they  wanted  to  drag  up  trees." 
He  and  other  authors  have  even  been  able 
to  testify  to  increased  potency.  As  I  have 
already  stated  above,  it  has  been  possible 
to  observe  these  specific  arsenic  effects 
with  atoxyl  and  atoxylate  of  mercury. 
True,  other  authors  have  also  reported 
marked  emaciation. 


6.  Effect  of  Arsenobenzol  on  Syphi- 
litic Diseases  of  the  Primary, 
Secondary,  and  Tertiary  Periods. 

The  first  reports  of  the  effect  of  arseno- 
benzol on  syphilitic  diseased  tissues  were 
made  by  Professor  Conrad  Alt,  of  Ucht- 
springe,  on  the  occasion  of  a  lecture  de- 
livered before  the  Magdeburg  Medical 
Society  in  March,  1910.  From  January  31, 
1910,  up  to  the  time  of  publication,  in 
common  with  Dr.  Schreiber  at  the  Magde- 
burg Old  Town  Hospital,  Alt  had  treated 
twenty-seven   cases    of   florid   syphilis    by 

89 


THE  THERAPY  OF  SYPHILIS 

means  of  a  single  injection  of  0*3  gramme 
of  the  new  preparation,  ''  and  has  had  quite 
startling  results  to  report/'  Alt  briefly 
summarises  the  facts  as  follows :  ''  The 
initial  sores  showed  marked  diminution  at 
the  end  of  a  few  days ;  the  indurating 
action  was  also  reduced ;  the  maculo- 
papulous  eruptions,  which  were  partly  of 
a  moist  and  ulcerating  character,  had  be- 
come paler  in  colour  or  had  dried  up,  and 
then  healed,  leaving  behind  fiat  pigment 
flakes.  Ulcerations  on  the  labia  healed 
quite  smoothly  within  a  few  days.  Large, 
swollen  papules  on  the  anus  and  vagina  lost 
colour  and  flattened  very  soon,  and  in  a 
few  specially  severe  cases  disappeared  with- 
out leaving  a  trace  behind  after  four  weeks' 
treatment.  Further,  a  very  large,  obstinate 
tertiary  ulcer  on  the  thigh  is  now  almost 
completely  cicatrised  after  hardly  three 
weeks'  treatment.  The  numerous  cases  of 
specific  angina  with  difficult  coatings,  which 
are  generally  very  obstinate,  were  reduced 
most  rapidly.'* 

90 


THE  CHEMOTHERAPY  OF  SYPHILIS 

According  to  the  first  reports  of  Wechsel- 
mann,  even  with  the  most  sceptical  criti- 
cism there  could  no  longer  be  any  doubt 
as  to  the  rapid  and  fundamental  action  of 
the  new  drug  on  the  symptoms  of  syphilis 
in  all  their  infectious  forms,  in  a  way  that 
had  been  impossible  with  any  previously 
known  remedy.  "  The  curative  effects  are 
so  rapid  that  the  patients  cannot  be  ex- 
hibited, because  generally  after  a  few  days 
there  is  nothing  more  to  demonstrate,  and 
they  leave  the  hospital/' 

Unfortunately,  the  great  expectations 
were  only  partly  fulfilled,  which  were  antici- 
pated for  this  drug,  as  the  result  of  the 
first  enthusiastic  and  favourable  reports 
of  Alt,  Wechselmann,  and  others.  The 
longer  the  observation  period  of  the  cases 
treated  lasted,  and  the  more  teachers 
received  arsenobenzol  for  the  treatment  of 
syphilis,  the  more  was  it  recognised  that 
this  new  arsenic  preparation  of  Ehrlich's, 
although  it  is  true  it  developed  a  very 
good  therapeutic  action  on  manifest  syphili- 

91 


THE  THERAPY  OF  SYPHILIS 

tic  symptoms  in  most  cases,  did  not  effect 
a  complete  cure  of  syphilis  in  the  sense 
Ehrlich  anticipated,  and  certainly  this  cannot 
be  obtained. 

If  we  group  together  the  opinions  of  the 
teachers  who  have  been  able  to  work 
v/ith  this  preparation,  and  the  results  of 
their  experience  with  it,  reported  up  to  the 
present,^  regarding  the  therapeutic  effect  of 
arsenobenzol  on  the  forms  of  disease  of  the 
various  syphilitic  periods,  the  result  is  as 
follows  : 

{a)    PRIMARY  AFFECTIONS. 

As  we  have  already  seen,  Alt  states  that 
the  primary  sores  were  markedly  reduced 
within  a  short  time,  the  indurations  dis- 
appearing after  a  few  days.  With  one 
patient,  who  was  injected  by  Wechsel- 
mann  on  July  i8,  1910,  for  about  twenty 
roseola  specks  on  the  trunk,  and  a  greasy 
crusted  erosive  chancre  on  the  penis,  the 
chancre  was  already  clean  by  the  follow- 

^  Up  to  the  beginning  of  December,  1910. 
92 


THE  CHEMOTHERAPY  OF  SYPHILIS 

ing  day,  almost  without  induration,  and 
on  June  22,  it  was  closed  down  to  a  residue 
the  size  of  a  lentil.  With  the  same  patient, 
a  destructive  deep-seated  primary  affec- 
tion, the  size  of  a  five-shilling  piece, 
situated  in  the  lower  lip,  together  with  a 
maxillary  bubo  the  size  of  a  goose's  egg, 
had  been  anointed  in  May,  at  first  without 
an}^  great  effect.  On  Ma\^  20,  0-4  gramme 
of  ''Ehrlich-Hata"  was  injected  intramus- 
cularly. On  June  2,  the  ulcer  was  flat,  the 
size  of  a  penny,  and  the  gland  was  quite 
small  and  almost  healed  on  June  8.  In 
cartilaginous  primary  forms,  in  the  experi- 
ence of  Wechselmann,  Miekley,  and  others, 
the  cleansing  process  proceeds  very  rapidly, 
but  the  complete  cure  lasts  longer,  corre- 
sponding to  the  absorption  of  the  tissue 
proliferation.  According  to  Dorr,  Ivensen, 
Juliusberg,  Schreiber,  and  Zeissl,  the 
phenomena  of  the  primary  affection  are 
rapidly  reduced,  generally  more  quickly 
than  with  Hg.  Neisser  has  seen  the  rapid 
disappearance  of  the  primary  symptom^s  in 

93 


THE  THERAPY  OF  SYPHILIS 

many  cases,  and,  further,  the  curative 
results  of  ChrzeHtzer,  Miekley,  Bethmann, 
and  others  were  surprising  in  this  direction. 
Spatz  stated  that  ulcerous  primary  forms 
were  skinned  over  and  softened  within  six 
days.  Geronne  and  Huggenberg  reported 
that  ten  ulcera  dura,  the  size  of  sixpences, 
had  closed  up  within  ten  to  fourteen  days. 
According  to  Solomon,  also,  the  average 
cure  of  the  primary  affection,  when  treated 
with  ''  606,''  was  effected  in  a  similar  period. 
Herxheimer  considers  that  the  primary 
affection  requires  on  an  average  eight  to 
fourteen  days  to  disappear.  In  four  cases, 
however,  the  indurations  remained  almost 
unchanged  during  the  iirs'''  three  weeks. 
Grouven  and  Frankel  saw  the  primary 
affection  frequently  recede  within  a  few 
days.  Pinkus  considered  that,  on  an 
average,  nine  days  was  required  for  this. 
Iversen,  however,  reported  that  primary 
sclerosis  and  glandular  swellings  persisted 
the  longest  in  consequence  of  the  anatomical 
conditions,   but  then  became   softer,    and 

94 


THE  CHEMOTHERAPY  OF  SYPHILIS 

gradually  melted  away.  Their  complete 
disappearance  would  certainly  be  effected 
within  three  to  four  weeks.  Spiethoff  saw 
primary  syphilis  completely  epithelialised 
within  one  to  three  weeks.  Phimoses, 
which  had  appeared  as  the  result  of  primary 
affection,  receded  altogether  without  any 
local  treatment  in  about  three  weeks  with 
a  dose  of  0-3  gramme,  and  after  six  days 
with  one  of  0'6  gramme.  L.  Michaelis 
similarly  considers  that  an  injection  of 
''  606  "  is  quite  sufficient  to  cure  primary 
syphilis,  without  any  local  treatment,  with- 
in one  to  three  weeks.  Jadassohn  also 
saw  a  very  rapid  and  prompt  result  ob- 
tained on  the  primary  affection  with  arseno- 
benzol.  In  Welander's  experience,  the 
primary  affection  skins  over  very  rapidly, 
but  induration  persists  for  a  long  time. 
Geronne  later  came  to  a  similar  conclusion. 
Gennerich  also  was  able  to  testify  to  severe 
sclerosis  in  several  cases  even  after  three 
or  four  weeks,  whereas  superficial  primary 
forms   only  slightly  indurated  were   often 

95 


THE  THERAPY  OF  SYPHILIS 

skinned  over  and  softened  two  to  three 
days  after  the  injection.  Rille  found  that 
the  shortest  time  required  for  heahng  the 
primary  affection  was  seven  days,  the 
longest  twenty-four.  Pick  frequently  ob- 
served rapid  epithelialisation  of  exulcerated 
scleroses.  Schulz  reported  that  primary 
forms  healed  on  an  average  within  five  to 
eight  days  after  the  injection.  Halber- 
stadter  also  considers  that  here  there  is 
generally  a  prompt  and  rapid  retrogression. 
According  to  Duhot,  the  chancre  disap- 
pears within  three  to  thirteen  days,  having 
regard  to  whether  it  is  indurated  or  not. 
The  experience  of  Halberstadter,  Deneke, 
and  Schindler,  with  scleroses  of  the  lips, 
was  that  these  were  influenced  relatively 
slowly,  or  not  at  all,  by  the  new  prepara- 
tion. 

Less  favourable  results  of  the  effect  of 
arsenobenzol  on  primary  syphilis,  despite 
higher  doses  (0*5  to  07  gramme),  were  re- 
corded by  Stern,  who  was  obliged  to  have 
recourse  to  local  treatment  with  calomel. 

96 


THE  CHEMOTHERAPY  OF  SYPHILIS 

Sclerosis  of  the  portio  appears  to  be  most 
obstinate  in  resisting  the  curative  effect- 
In  nine  such  cases,  the  average  duration  of 
the  heahng  process,  according  to  Gliick, 
was  eighteen  days.  The  observation  of 
Sieskind  is  interesting,  that  after  the  dis- 
appearance of  the  scleroses  in  the  treat- 
ment of  chancres  mixtes,  ulcers  of  the 
character  of  tdacs  molle  still  remain  behind, 
which  are  uninfluenced  bv  arsenobenzol. 

Now,  how  does  the  case  stand  with 
regionary  syphilitic  lymphatic  glandular 
swellings,  which  are  known  to  appear  a 
short  time  after  the  primary  affection,  and 
even  before  the  outbreak  of  the  general 
phenomena  ?  From  my  experience,  and 
that  of  most  other  authors  (Blumen- 
feld,  Schulz,  von  Zeissl),  these  are  in  part 
very  favourably  influenced  therapeutically 
by  the  new  preparation.  Blumenfeld  re- 
cords a  case  of  strumous  bubo,  which 
diminished  within  eight  days  to  about  a 
fifth  of  its  original  size.  True,  it  is 
but  seldom  that  it  disappears  altogether. 

97  G 


THE  THERAPY  OF  SYPHILIS 

Pinkus  states  that  a  diminution  of  the 
regionary  lymphatic  glands  can  regularly 
be  observed,  but  without  these  disappearing 
completely.  In  most  cases  lymphatic  cords 
and  smaller  lymphatic  glandular  swellings 
are  left  behind  (Geronne  and  Huggenberg). 
In  Miekley's  experience,  on  the  other  hand, 
these  glands  only  recede  very  gradually  ; 
apparently  they  are  the  slowest  to  be  in- 
fluenced of  all  the  diseased  tissues. 

{b)    EARLY  STAGE   OF  SECONDARY   SYPHILIS. 

It  appears  from  the  results  and  opinions 
of  most  teachers,  that  the  most  favourable 
influence  of  arsenobenzol  is  obtained  upon 
the  phenomena  of  the  secondary  stage  of 
syphilitic  diseased  tissues  of  the  mucous 
membranes.  Spiethoff  saw  mucous  plaques 
completely  disappear  two  to  three  days 
after  the  injection.  According  to  the 
statements  of  G6ronne  and  Huggenberg, 
in  specific  angina  the  plaques  healed  within 
seven  to   ten   days.     Isaac   also   observed 

98 


THE  CHEMOTHERAPY  OF  SYPHILIS 

similarly  rapid  healing  of  plaques  and 
condylomata  of  the  mucous  membrane. 
Severe  erosive  and  papulous  diseases  of 
the  mucous  membrane  reacted  specially 
sympathetically,  while  a  previous  mercurial 
treatment  had  remained  without  result 
(Grouven  and  Frankel).  It  appears  from 
Miekley's  communications  that  the  coat- 
ings on  the  tonsils  melt  away  during  the 
first  days  following  the  injection,  so  that 
this  may  be  compared  to  the  effect  of 
Behring's  serum  on  diphtheritic  surfaces. 
The  splitting  and  moderate  hyperplasia 
of  the  tonsils  remaining  soon  disappear. 
Frequently  on  the  eighth  day  after  in- 
jection the  angina  is  perfectly  cured.  Ac- 
cording to  the  observations  of  Gliick,  it  is 
only  the  redness  of  the  pharyngeal  organs 
which  persists  so  long,  while  the  plaques 
on  the  tongue,  tonsils,  and  soft  palate 
have  disappeared  at  latest  five  days  after 
the  injection.  In  specific  hoarseness  the 
voice  has  cleared  three  to  eight  days  after  the 
injection  (Blumenfeld,  Gliick,  and  others). 

99 


THE  THERAPY  OF  SYPHILIS 

The  effect  of  the  injection  of  arseno- 
benzol  was  equally  rapid  in  simple  macu- 
lated exanthemata  (Wechselmann,  L. 
Michaelis,  Kromayer,  Spiethoff,  Spatz, 
Gennerich,  Dennecke,  Rille)  ;  they  generally 
disappeared  within  the  course  of  a  few 
days  (Brandle  and  Clingestein,  and  others). 
Miekley  alone  testified  to  the  surprisingly 
slow  softening  of  the  roseola,  pigment  of 
which  was  often  visible  several  weeks  after 
the  injection,  with  simultaneously  per- 
sisting hyperplasia.  Sieskind  confirmed 
this  statement  in  the  case  of  roseola 
urticata. 

Papulous  and  pustulous  syphilides  dis- 
appeared rapidly  and  dried  up  (Spiethoff, 
Dorr,  Iversen,  Miekley).  In  papulous  ex- 
anthema as  a  rule  a  slight  pigmentation 
is  left  behind  (Chrzelitzer  and  others).  A 
papulous  crustaceous  exanthema  had  dried 
up  completely  at  the  end  of  two  days 
after  0'6  gramme,  and  the  crusts  had 
fallen  off  (Spiethoff).  According  to  Sies- 
kind, it   is   only   the   micropapulous   and 

100 


THE  CHEMOTHERAPY  OF  SYPHILIS 

lichenoid  exanthemata  respectively  which 
respond  to  a  certain  extent  favourably  to 
arsenobenzol ;  whereas  one  can  assert  of 
the  large  papulous  syphilides  that  they 
appear  to  be  refractory  to  "606."  Ulcer- 
ous syphilides  also,  and  even  rupice 
syphiliticcB,  can  be  rapidly  cured  (Isaac, 
Brandenburg,  Juliusberg).  Moist  papules 
dry  up  and  flatten  out,  often  in  a  short 
time  (Spatz,  Geronne  and  Huggenberg, 
Miekley),  but  still  they  may  persist  for 
a  fairly  long  time  (Welander,  Schreiber, 
Ledermann) .  Condylomata  form  new  skin 
visibly,  and  often  disappear  with  almost 
miraculous  rapidity  (Grouven  and  Frankel) . 
An  excellent  therapeutic  effect  has  been 
obtained  with  arsenobenzol,  according  to 
Volk  and  Lipschiitz,  in  renitent  syphilitic 
paronychia.  Psoriasis  palmaris  and  plan- 
taris  had  disappeared  at  the  end  of  ten 
days  (Geronne  and  Huggenberg,  Saalfeld), 
but  Bruhns  stated  that  several  cases  of 
specific  psoriasis  had  been  very  obstinate. 
Wechselmann  once  saw  a  leucoderma   colli 

lOI 


THE  THERAPY  OF  SYPHILIS 

disappear  within  a  few  days,  while  the 
white  places  healed  up.  In  contradistinc- 
tion to  this,  there  are  the  observations  of 
Volk  and  Lipschiitz,  among  others,  that 
leucoderma  especially  remained  uninflu- 
enced by  "  Ehrlich-Hata/' 

Generalised  lymphadenitis,  as  well  as 
isolated  glands  in  the  secondary  stage, 
may  disappear  within  the  course  of  a  few 
days  (Dorr,  Spiethoff,  Sieskind),  or  at  least 
show  a  marked  inclination  to  recede  (Hoff- 
mann, Grouven,  and  Frankel).  On  the 
other  hand,  in  the  experience  gained  at  the 
Lesser  Clinique,  it  is  especially  the  glands 
in  the  secondary  stage  which  are  longest 
in  reacting  to  the  influence,  as  already 
mentioned. 

A  haemorrhagic  exanthema  of  the  leg  re- 
ceded at  the  end  of  eighteen  days  ;  a  severe 
impetiginous  syphilide  under  the  hair  of 
the  head,  and  one  on  the  back,  disappeared 
after  sixteen  and  twenty-one  days  respec- 
tively (Geronne  and  Huggenberg). 

Headache,   the  appearance  of  which  is 

102 


THE  CHEMOTHERAPY  OF  SYPHILIS 

specially  characteristic  of  secondar}^  syphilis, 
often  disappears  at  the  end  of  twenty- 
four  hours  (Blumenfeld,  Neisser,  Halber- 
stadter,  Sieskind).  Syphilitic  bone  disease 
reacts  promptly,  according  to  the  experi- 
ence of  Sieskind  and  others. 

The  most  difficult  to  influence  are  appar- 
ently anal  papules  (Brandle  and  Clinge- 
stein)  and  hypertrophic  papules  (Volk  and 
Lipschiitz),  as  well  as  more  severe  papulous 
exanthemata  (Hoffmann),  especially  the 
hard  cutaneous  papules,  which,  in  Wechsel- 
mann's  experience,  onh^  disappear  at  the 
end  of  two  to  three  wrecks. 

Most  authors,  as  is  evident  from  the 
foregoing  references,  are  able  to  testify  to 
very  good  results,  as  regards  the  momentary 
curative  effect,  especially  with  the  diseased 
tissue  of  early  secondary  syphilis.  In 
the  experience  of  other  teachers,  however, 
the  clinical  phenomena  of  this  period  did 
not  disappear  mth  such  striking  rapidity 
(Bruhns).  In  some  instances  the  effects 
were  slow  and  unsatisfactory  (Kromayer), 

103 


THE  THERAPY  OF  SYPHILIS 

and  often  not  more  rapid  than  with  Hg 
treatment  (Saalfeld,  Ledermann,  Buschke, 
Volk,  Blaschko,  and  Lipschiitz). 

In  the  treatment  of  certain  cases  in  the 
early  secondar}^  period,   the    phenomenon 
of    the    Jarisch-Herxheimer    reaction    was 
mostly  observed  (by  Trufh,  Wechselmann, 
Neisser,    Herxheimer    [in    60    per    cent.], 
Chrzelitzer,       Kromayer,       Halberstadter, 
Wolters,   Volk  and   Lipschiitz,   Hoffmann, 
myself,  and  others).     This  phenomenon  is 
known   from   mercurial   therapy,    and   ex- 
presses itself  chiefly  in  the  fact  that  often 
twenty-four     to    forty-eight    hours     after 
mercurial  treatment  has  been  inaugurated 
there  is  an  increase  of  the  existing  exan- 
themata.    Before    the    discovery    of    the 
5.     pallida,    this    circumstance    was    fre- 
quently   brought    forward    for    diagnostic 
purposes,   in  order  to   determine  whether 
isolated   flakes   present,    which   were   only 
just  visible,  might  be  pronounced  as  roseola 
or  not.     Ehrlich  regards  the   Herxheimer 
reaction    in    the    *'  606 "    treatment     and 

104 


THE  CHEMOTHERAPY  OF  SYPHILIS 

similar  phenomena  as  an  inadequate  action 
of  the  injection.  In  his  opinion,  in  such 
cases  the  parasites  are  not  at  once  de- 
stroyed, but,  instead,  only  irritated,  and 
in  this  condition  produce  an  increased 
quantity  of  toxines.  If  the  Herxheimer 
reaction  appears  in  exanthemata,  Sieskind 
beheves  that  it  must  be  regarded  prognos- 
tically  as  an  unfavourable  sign. 

Besides  this  ''  local ''  reaction,  A.  Neisser 
distinguishes  a  ''  general "  one  in  the 
treatment  with  arsenobenzol,  which  is 
characterised  b}^  transitory  increase  of  the 
headache  in  cerebral  syphilis,  and  of  the 
irritant  spinal  phenomena  in  tabes. 

In  treating  syphilitic  infected  tissues  of 
the  primary  and  secondary  periods,  it  is 
naturally  of  great  interest  and  importance, 
in  estimating  the  effect  of  arsenobenzol, 
to  study  the  behaviour  of  the  spirochaetes 
after  one  injection.  In  many  of  these  forms 
of  disease  they  can  be  distinguished  more 
or  less  easily,  and  generally  in  greater 
numbers.     (In  the  tertiary  and  malignant 

105 


THE  THERAPY  OF  SYPHILIS 

forms  it  is  known  that  this  does  not  suc- 
ceed, or  only  very  rarely.) 

By  means  of  animal  experiments  (Hata, 
Tomasczewski,  Uhlenhuth,  and  the  author) 
we  know,  as  already  mentioned  above,  that 
the  spirochsetes  have  disappeared  from  the 
infected  tissue  of  experimental  syphilis  and 
of  spirillosis  of  fowls  sixteen,  twenty-four, 
or  thirty-six  hours  after  the  injection  of 
the  dose  of  arsenobenzol.  In  man,  accord- 
ing to  Sieskind,  Schreiber,  Sellei,  and 
Gliick,  they  mostly  disappear  at  the  end 
of  a  day  from  the  manifested  phenomena 
of  primary  and  secondary  syphilis.  If 
spirochsetes  can  still  be  detected  on 
the  second  day  after  the  injection,  these 
appear  swollen  and  altered  in  their 
motility. 

According  to  Spiethoff's  observations, 
the  spirochsetes  disappear  from  the  irritant 
serum,  on  an  average,  twenty-four  to  forty- 
eight  hours  after  the  injection.  In  thirty- 
two  carefully  controlled  cases,  Scholtz  saw 
the  spirochaetes  disappear  permanently  at 

io6 


THE  CHEMOTHERAPY  OF  SYPHILIS 

the  end  of  twenty-four  hours  fifteen  times  ; 
twelve  times  they  could  be  detected  for 
two  to  three  days  ;  and  only  five  times 
were  they  evident  longer  than  four  days. 
Iversen  punctured  the  glands  in  ten  cases 
of  very  pronounced  primary  lymphadenitis 
a  few  days  before  treatment  with  ''606'' 
as  well  as  a  few  days  after.  In  all  these 
cases,  he  was  unable  to  discover  any  spiro- 
chaetes  in  the  glandular  juices  three  to 
five  days  after  the  injection,  whereas 
before  they  had  been  present  in  great 
numbers. 

True,  Hoffmann  proved  that  in  a  series 
of  cases  spirochaetes  were  not  evident  on 
the  surface  of  papules  and  plaques  after 
twenty-four  to  seventy-two  hours.  He 
had,  however,  seen  cases  where  they  were 
still  to  be  found  in  perfect  motility  on  the 
genital  and  tonsillar  papules  at  the  end  of 
eight  days. 

In  one  case  of  papules  of  the  mouth  and 
anus,  which  had  reappeared  twelve  days 
later,  despite  a  successful  Ehrlich-Hata  in- 

107 


THE  THERAPY  OF  SYPHILIS 

jection,  Oppenheim  found  numerous  well- 
preserved  PallidcB.  According  to  Bruhns, 
in  many  cases  the  spirochsetes  had  already 
disappeared  at  the  end  of  two  days, 
whereas  in  others  they  were  still  present 
later.  Grouven  was  able  to  prove  the 
presence  of  living  well-preserved  spiro- 
chsetes in  a  facial  papule  at  the  end  of 
two  months. 

Fiirth,  in  sclerosis  of  the  urethral  orifice, 
saw  lively  mobile  spirochaetes  seven  da5/s 
after  an  arsenobenzol  injection,  and  after 
the  chancre  had  healed. 

If  at  the  end  of  twenty-four  to  forty- 
eight  hours  the  spirochsetes  have  not  yet 
disappeared,  this,  in  the  opinion  of  Ehrlich, 
is  an  indication  that  either  the  dose  was 
too  small,  that  the  absorption  was  in- 
adequate, or  that  one  had  to  do  with  an 
arsenic-fast  strain  of  spirochsetes. 

Hecker  only  attributes  slight  importance 
to  the  negative  spirochsete  result  in  specific 
efflorescences  a  few  days  after  the  injection 
of  Ehrlich-Hata  ''  606."     Although  in  some 

108 


THE  CHEMOTHERAPY  OF  SYPHILIS 

of  the  cases  he  treated  the  spirochaetes  dis- 
appeared promptly,  a  little  later  relapses, 
with  numerous  spirochaetes,  set  in  at  these 
places. 

Moreover,  in  two  cases  of  congenital 
syphilis  in  which  the  patients  died  two 
and  four  days  after  the  injection  of  arseno- 
benzol  respectively,  Herxheimer  found  no 
specific  spirochaetes  in  any  of  the  organs, 
with  the  exception  of  the  lungs.  Here,  the 
spirochaetes  appeared  to  be  agglutinated 
and  degenerated  to  the  fullest  extent  up 
to  complete  disintegration.  Herxheimer 
considers  that  the  enormous  syphilitic 
spirochaeticide  action  of  the  new  drug  is 
especially  demonstrated  in  these  two  cases, 
in  that  a  large  quantity  of  spirochaetes  are 
almost  constantly  found  in  the  internal 
organs  in  cases  of  congenital  syphilis. 

Gerber  was  able  to  testify  to  the  dis- 
tinctly destructive  influence  of  arseno- 
benzol  on  the  spirochaetes  of  the  mouth  in 
one  case  of  severe  tertiary  syphilis.  Refer- 
ence must  also  be  made  to  the  spirillicide 

109 


THE  THERAPY  OF  SYPHILIS 

effect  of  this  preparation  in  the  curative 
results  obtained  with  ''  606 ''  in  Plaut- 
Vincent's  angina  (Rumpel), 

(c)     THE    LATE    STAGE    OF    SECONDARY 
SYPHILIS   AND   TERTIARY   SYPHILIS. 

It  is  just  in  these  periods  that  the  most 
obstinate  forms  of  the  disease  often  occur, 
which  are  either  uninfluenced  by  specific 
mercurial  or  iodine  therapy,  even  when  ad- 
ministered in  the  strongest  doses,  or  are 
only  affected  very  slightly  and  slowly.  In 
the  manifold  and  frequently  severe  dis- 
turbances of  tertiary  syphilis,  the  thera- 
peutic action  of  the  new  Ehrlich  preparation 
is  generally  found  to  be  most  effective. 
Wechselmann  gives  the  following  report  of 
the  excellent  effect  of  arsenobenzol  in  one 
case  : 

A  patient  had  developed  the  primary 
symptoms  seven  months  previously,  and 
an  eruption  appeared  four  weeks  later. 
From  November  28,   1909,   to  the  middle 

no 


THE  CHEMOTHERAPY  OF  SYPHILIS 

of  March,  1910,  he  was  given  thirty-five 
injections  of  hydrarg.  sal  and  calomel.  For 
three  months  he  had  had  pain  in  the  joints 
of  both  knees.  On  May  5,  1910,  he  came 
under  Wechselmann's  treatment.  **  The 
patient  is  emaciated  to  a  skeleton ;  his 
skin  is  as  pale  as  a  corpse,  and  his  face 
like  a  death's-head,  with  an  intensely 
painful  expression."  On  the  face  and  body 
there  were  ulcers  and  cicatrices  the  size 
of  sixpence  (ten  pfennige),  and  even  bigger, 
covered  with  crusts,  and  extending  down 
to  the  subcutaneous  cellular  tissue.  An 
odious  smell  proceeded  from  the  nose,  in 
which  the  septum  was  perforated,  and  the 
left  lower  muscle  and  vomer  were  about 
to  be  shed.  He  had  intense  pain  in 
swallowing,  and  had  to  be  fed  with  pharjm- 
geal  probes  and  nutrient  enema.  The 
pulse  was  very  small,  with  bad  tension, 
and  was  120  and  more.  As  his  condition 
constantly  deteriorated  under  iodine  in- 
jections, and  a  fatal  issue  was  anticipated 
within  a  conceivable  time,  he  was  injected 

III 


THE  THERAPY  OF  SYPHILIS 

by  Wechselmann  on  May  21,  with 0*4  gramme 
"  Ehrlich-Hata."  This  was  not  followed 
by  any  rise  of  temperature,  and  the  pain 
remained  moderate.  Even  at  the  end  of 
two  to  three  days  the  patient's  general 
condition  had  improved  distinctly,  and  on 
May  26,  general  recovery  began.  The 
diseased  bony  nasal  framework  fell  off 
altogether,  and  the  foetor  disappeared. 
On  May  30,  the  ulcers  were  responding  per- 
fectly to  the  healing  process,  or  were  com- 
pletely healed.  The  patient  had  increased 
in  weight  from  41*5  kilos  on  May  21,  to 
49  kilos  on  June  22  (according  to  Bressler). 
An  equally  brilliant  result  is  recorded  by 
Michealis  in  one  case  :  A  patient  became 
infected  in  1906,  and,  despite  treatment  in 
1907  with  mercury,  atoxyl,  and  iodide  of 
potassium,  ulcers  appeared  in  the  gums  on 
the  right  and  left  of  the  uvula,  and,  further, 
a  saddle-nose  had  developed.  The  uvula 
was  only  hanging  by  a  stalk,  ''  and  it 
might  drop  off  any  day."  Three  days 
afterwards  the  surroundings  of   the   walls 

112 


THE  CHEMOTHERAPY  OF  SYPHILIS 

of  the  ulcers  were  red,  and  eight  days  after 
the  injection  only  small  fragments  of  the 
former  ulcers  remained  on  both  sides  of 
the  uvula.     In  two  cases  of  very  extensive 
ulceration  of  the  thigh  and  subcutaneous 
gummata  with  exposed  bones,  Kromayer 
observed  an  extraordinarily  rapid  absorp- 
tion of  the  infiltration  and  quick  skinning 
over   of  the  ulcers.      ^'  The   epithelisation 
occurred  in  a  formerly  unknown  manner/' 
According  to  Iversen,  an  excellent  curative 
effect  is  shown  especially  in  ulcerous  pro- 
cesses, gummata,  and  gummatous  wounds. 
Gliick  reports  that  in  three  cases  of  gum- 
mata of  the  larynx  an  injection  of  arseno- 
benzol  practically  saved  the  patients'  lives. 
Spiethoff  records  one  case  of  tertiary  nasal 
syphilis  in  which,  twenty-four  hours  after 
an  injection  of  0*6  gramme  of  *'  606,''  the 
purulent  secretion  of  a  disintegrated  gumma 
located   in   a   muscle   ceased.      The    ulcer 
had  closed  by  the  second  day,  and  only 
slight    infiltration    remained.      A    patient 
who  had  been  antisyphilitically  treated  in 

113  H 


THE  THERAPY  OF  SYPHILIS 

several  ways  from  1906,  and  was  now 
suffering  from  an  unusually  large  gum- 
matous ulcer,  was  injected  by  Ledermann 
with  0'5  gramme  of  Ehrlich's  preparation. 
The  necrotic  eschar  of  the  ulcer  fell  off 
the  day  after  the  injection  ;  two  days  later 
the  skinning  over  began ;  and  on  the 
thirteenth  day  half  of  the  ulcer,  which 
was  the  size  of  a  hand,  was  closed.  The 
epithelial  margin  pushed  forward  daily  from 
I  to  I  c.c. 

Herxheimer  treated  nine  cases  of  re- 
tarded (secondary)  syphilitic  phenomena 
(tuberous  syphilides  and  gummata).  Peri- 
ostitis of  the  vault  of  the  cranium  disap- 
peared after  seven  days  (there  was  intense 
swelling  on  the  fourth  day)  ;  a  gumma 
of  the  left  tonsil  disappeared  in  six  days 
after  0*3  gramme ;  multiple  gummata  of  the 
hard  and  soft  palates  in  ten  days  after 
0*45  gramme.  An  ulcerated  gumma  of  the 
left  testicle,  the  size  of  the  fist,  receded 
rapidly  at  the  end  of  twenty-four  hours, 
after  0*5  gramme  (the  patient  had  tubercle 

114  . 


THE  CHEMOTHERAPY  OF  SYPHILIS 

of  both  lungs).  A  gummatous  disintegrated 
hard  and  soft  palate,  which  had  been 
refractory  to  mercurial  and  iodine  treat- 
ment for  seven  years,  healed  so  rapidly 
that  at  the  end  of  a  week  the  patient  could 
again  eat  solid  food,  and  at  the  end  of  three 
weeks  there  were  only  quite  small  frag- 
ments remaining. 

In  one  case  of  testicular  and  cerebral 
syphilis,  Wechselmann  was  able  to  effect  a 
cure  in  about  four  days  after  an  injection 
of  0-405  gramme  of  ''  606."  Geronne  and 
Huggenberg  saw  an  orchitis  gummosa,  the 
size  of  a  small  fist,  shrink  almost  to  the 
size  of  the  healthy  testicle  within  sixteen 
days  after  the  injection.  Isaac  stated  that 
a  serpigino-ulcerous  syphilide,  which  had 
appeared  four  years  after  the  infection,  to- 
gether with  disintegrated  gummata  on  the" 
roof  of  the  larynx  and  papules  on  the 
vulva  and  anus,  healed  completely  within 
ten  days  of  the  injection. 

Meirowsky,    amongst    other    things,    re- 
cords  the   prom.pt   cure   of  large   tertiary 

115 


THE  THERAPY  OF  SYPHILIS 

ulcers  of  the  hard  palate  and  of  the  vault 
of  the  cranium  after  the  injection  of  arseno- 
benzol.  Wolters  describes  the  influence 
of  the  Ehrlich  preparation  on  advanced 
forms  of  syphilis  as  generally  startling. 
''  Ulcerated  gummata  heal  in  a  surprisingly 
short  time.  Bony  processes,  after  a  very 
energetic  reaction  (pain),  at  first  show  a 
slow  but  constant  recovery.''  Aschaff en- 
burg  and  Gesser  were  able  to  testify  to  a 
brilliant  result  in  a  case  of  cerebral  syphilis. 
According  to  the  reports  of  von  Zeissl, 
gummata  of  the  mucous  membrane  of  the 
mouth,  tongue,  and  throat  clear  up,  so  that 
patients  can  soon  take  solid  and  liquid  food 
without  hesitation.  Cutaneous  malignant 
syphilis  (one  large  and  one  small  gumma- 
matous  syphilide)  healed  rapidly  under 
''  606,''  whereas  the  previous  injections 
with  insoluble  Hg  had  remained  unsuccess- 
ful. Periostitis  of  the  end  of  the  radius, 
which  was  of  some  years'  standing,  dimin- 
ished visibly  within  four  days,  and  the 
pain  disappeared  altogether. 

116 


THE  CHEMOTHERAPY  OF  SYPHILIS 

Ehrlich  himself  records  one  case  which 
shows  very  markedly  the  rapid  action  of 
arsenobenzol  in  diseases  of  the  pharyngeal 
organs  :  *^  A  patient  with  gumma  of  the 
tonsil,  who  for  two  months  had  been 
treated  without  result,  was  given  an  in- 
jection at  two  o'clock ;  five  hours  later 
the  medical  man  was  able  to  testify  to 
the  fact  that  the  patient,  to  his  great  joy, 
had  been  able  to  swallow  a  piece  of  bread- 
and-butter  without  pain." 

Chrzelitzer  sav/  a  laryngeal  gumma 
disappear  at  the  end  of  four  days.  Fried- 
lander  reported  the  extraordinarily  suc- 
cessful result  of  this  treatment  in  fifteen 
cases  of  severe  ulcerations  and  gummatous 
processes  in  the  mouth,  nose,  larynx,  and 
trachea. 

Weber  was  able  to  report  a  very  good 
result  in  a  case  of  severe  cerebral  syphilis 
and  specific  meningitis.  Within  a  few 
days  recovery  took  place,  and  the  markedly 
disturbed  pupillary  reflex,  speech,  and 
power    of    movement    of    the    right    side 

117 


THE  THERAPY  OF  SYPHILIS 

returned,  as  well  as  complete  mental  power. 
Gennerich  found,  from  experience,  that 
cerebral  syphilis  offered  a  specially  favour- 
able domain  for  Ehrlich-Hata  treatment. 
"  In  many  cases  here  it  is  life-saving ;  in 
others  it  preserves  whatever  there  is  to 
preserve.''  In  one  case  of  cerebral  syphilis 
[arteritis  obliterans)  I  observed  and  treated, 
it  was  not  possible  to  save  the  patient  with 
an  injection  of  0*5  gramme  arsenobenzol. 
It  is  true  the  case  was  very  far  advanced  in 
the  secondary  period,  with  flabby  paralysis 
of  the  left  side,  as  well  as  facial  paralysis. 
Miekley  has  also  seen  extraordinarily  favour- 
able results  in  the  treatment  of  tertiary 
syphilis.  Thus,  a  muscular  gumma  on  the 
ulnar  side  of  the  left  forearm,  which  was 
the  size  of  a  large  goose's  egg,  diminished 
to  that  of  a  pigeon's  egg  four  to  five  days 
after  the  injection,  and  healed  completely 
in  under  fourteen  days.  Tertiary  ulcers  of 
the  leg  only  required  a  week  and  a  half  for 
complete  cure.  A  deep  ulcerous  thrombo- 
phlebitis  of   the   knee   diminished   within 

118 


THE  CHEMOTHERAPY  OF  SYPHILIS 

fourteen  days  to  the  size  of  a  sixpence  (ten 
pfennige).  Miekley,  as  the  result  of  these 
observations,  summarises  his  opinion  of  the 
effect  of  arsenobenzol  on  tertiary  syphihs 
as  follows  :  ''  The  graver  the  case,  the  more 
surprising  the  effect/' 

In  the  experience  of  Zieler,  Bayet,  and 
others,  on  the  other  hand,  it  is  not  always 
possible  to  prove  the  superiority  of  arseno- 
benzol over  mercury  in  tertiary  syphilis. 
Thus,  Zieler  states  that  out  of  thirteen 
such  cases,  only  four  were  favourably 
influenced. 


{d)    MALIGNANT    SYPHILIS   AND    ULCEROUS 
TERTIARY   FORMS   RESPECTIVELY. 

-  The  same  thing  appears  to  apply  to 
malignant  syphilis  and  early  ulcerous 
syphilis  respectively,  as  has  been  said  of 
the  curative  effect  of  arsenobenzol  in 
tertiary  forms. 

According  to  the  researches  of  Grouven, 
Hoffmann,     Ledermann,     Juliusberg,    and 

119 


THE  THERAPY  OF  SYPHILIS 

most  other  authors,  mahgnant  syphilis  is  in- 
fluenced equally  favourably.  In  two  cases 
of  malignant  syphilis,  in  one  of  which 
a  fatal  prognosis  had  been  given,  Dorr 
also  saw  excellent  results,  both  with  regard 
to  the  cure  of  the  infected  processes  as 
well  as  in  marked  improvement  of  the 
general  condition.  Pick  observed  the  dis- 
appearance of  the  symptoms  (of  pharyneal 
ulcer  and  gumma,  and  papules  of  the  tonsil, 
respectively)  a  few  days  after  the  injection, 
in  two  cases  of  malignant  syphilis,  in 
which  iodine  and  mercury  had  been  in- 
effectual. Grouven  and  Frankel  perceived 
the  influence  of  arsenobenzol  treatment 
especially  distinctly  in  a  case  of  extensive 
ulcerous  formations  on  the  leg,  which 
skinned  over  and  cicatrised  in  the  very 
shortest  time.  Brandle  and  Clingestein 
obtained  most  excellent  results,  especially 
in  the  treatment  of  malignant  syphilis. 
As  Herxheimer  has  mentioned,  three  cases 
of  malignant  syphilis  responded  very  well. 
In  one  of  these  cases,  large  ulcers  of  the 

120 


THE  CHEMOTHERAPY  OF  SYPHILIS 

entire  skin  of  the  head,  of  the  hard  palate, 
the  throat,  and  tongue,  healed  in  ten  days 
with  0'4  gramme,  without  local  treatment. 
From  the  report  of  375  cases  treated  with 
the  Ehrlich-Hata  preparation,  collected  by 
Sieskind,  it  appears  that  symptoms  of 
malignant  s^^philis  and  lues  prsecox  offer 
the  most  gratifying  field  for  treatment  with 
*'  606,"  therefore  just  those  cases  which 
are  commonly  known  as  the  gravest  in 
syphilis.  Meirowsky,  on  the  other  hand, 
was  unable  to  distinguish  the  slightest  thera- 
peutic effect  after  the  intravenous  injection 
of  0*4  gramme  arsenobenzol  in  one  case 
of  malignant  syphilis.  Relapses  were  ob- 
served in  three  cases  of  malignant  syphilis 
by  Gennerich.  One  directly  unfavourable 
effect  of  the  Ehrlich-Hata  treatment  was 
seen  by  Fischer  in  a  case  of  this  description, 
which  was  also  refractory  to  all  Hg  and 
iodine  therapy. 

For  the  rest,  it  is  remarkable  that 
apparently  the  best,  and  perhaps  also  the 
most    lasting,    effect    of    arsenobenzol    is 

121 


THE  THERAPY  OF  SYPHILIS 

testified  to  in  the  tertiary  and  malignant 
forms  of  syphilis  respectively,  although  in 
these  products  one  can  never,  or  at  most 
only  very  rarely,  verify  the  presence  of 
isolated  spirochaetes.  In  my  opinion,  the 
principal  part  is  played  here  by  the  re- 
hounding  factor  of  the  arsenic  preparation, 
which  excites  the  tissue  to  fresh  activity. 

{e)    TREATMENT   OF   SYPHILITIC   DISEASES 
OF   THE   EYES   WITH   ARSENOBENZOL. 

I  should  like  to  class  together  in  a  par- 
ticular group  the  cases  of  specific  diseases 
of  the  eyes  which  have  been  treated  with 
Ehrlich-Hata  ''  606/'  After  the  experi- 
ence with  atoxyl  and  other  arsenic  prepara- 
tions, it  was  precisely  here  that  one  feared 
there  might  be  an  occasional  unfavourable 
effect  of  the  arsenobenzol.  Sieskind  saw 
four  cases  of  iritis  papulosa  promptly  im- 
proved. Gliick  treated  two  cases  of  specific 
ophthalmic  disease  (keratitis  parenchy- 
matosa  and  iritis)  with  very  good  success. 

122 


THE  CHEMOTHERAPY  OF  SYPPHLIS 

Von  Zeissl  saw  a  case  of  iritis  disappear 
four  days  after  the  injection  ;  a  paresis  of 
the  accommodation  was  very  favourably 
influenced.  I  myself  saw  a  bilateral  specific 
iritis  with  posterior  synechia  disappear 
promptly  and  rapidly.  Fehr  and  Seelig- 
sohn  obtained  good  results  in  episcleritis 
and  iritis. 

Grosz  treated  eight  patients  with  fresh 
specific  disease  of  the  eyes,  amongst  them 
a  case  of  ulcus  durum  conjunctivce,  with 
arsenobenzol,  and  was  able  to  prove  that 
this  drug  is  very  effective  in  specific  oph- 
thalmic disease. 

Good  results  have  also  been  obtained  in 
hereditary  syphilitic  eye  affections  with 
Ehrlich  -  Hata  ''  606  "  by  Grosz,  Treupel 
and  others,  without  injury  to  the  optic 
nerves.  Schanz  has  successfully  treated  five 
cases  of  keratitis  parenchymatosa.  In  some 
cases  in  which  the  visual  nerves  were  not 
quite  intact  (fresh  neuritis  optica)  Wechsel- 
mann  has  even  employed  arsenobenzol  suc- 
cessfully without  arousing  any  kind  of  dis- 

12^ 


THE  THERAPY  OF  SYPHILIS 

turbances  in  the  disease  itself.  In  six  cases 
also  of  commencing  or  advanced  atrophy  of 
the  optic  nerves,  he  has  given  the  injections 
without  increasing  this.      Anscherlick  has 
also  twice  made  an  injection  of  ''  606  ''  in 
diseases  of  the  eyes  without  being  able   to 
perceive   that   the    optic   nerves   had  been 
injured  in  any  way.    Exudative  processes  of 
the  choroid  and  of  the  retina  respectively 
were  favourably  influenced.  In  one  case  of 
atrophy  of    the    optic    nerves,  Gliick  was 
unable    to    obtain    any    therapeutic  result. 
Neither  could  Igersheimer  discover  any  in- 
fluence on  the  corneal  process  in  a  case  of 
congenital  specific  corneal  disease,  after  an 
injection  of  0*4  gramme  of  ''  606,"  although 
the    Wassermann    reaction    was    negative. 
Wechselmann   calls    attention   to   the  fact 
that   in   over   1,400   cases,    which   he   has 
treated  with  arsenobenzol,  he  has  never  ob- 
served amaurosis  or  any  other  kind  of  dis- 
turbance of  the  visual  apparatus,  and  that 
even  with  the  great  number  of  injections 
which    have    been   made   by  now — in    his 

124 


THE  CHEMOTHERAPY  OF  SYPHILIS 

estimation,  20,000— nothing  of  the  kind  is 

known/ 

Despite  all  these  good  results  in  specific 
eye  diseases,   it  is,  in  my  opinion,  abso- 
lutely necessary  first  of  all  to  convince  one- 
self  that   the   visual  nerves  are  perfectly 
healthy  before  an  injection  of  arsenobenzol 
is  given.     Wechselmann  has  recently  ex- 
pressly demanded  that  there  should  be  a 
thorough  ophthalmological  examination  of 
the  eyes,  occasionally  from  the  specialist's 
side,    particularly   of   the   field   of   vision. 
Cases  in  which  the  optic  nerve  is  not  quite 
intact    would    be    better    excluded    from 
treatment  with  arsenobenzol,   for  reasons 
which  I  shall  mention  when  discussing  the 
secondary   effects   of   atoxyl,    especially   if 
there  is  a  question  of  repeating  the  injec- 
tions.    One  must  wait  to  see  whether  this 
will  not  cause  injuries  of  the  optic  nerve, 
like  atoxyl ;  as  far  as  my  knowledge  goes, 
it  is  only  after  protracted  atoxylic  treat- 
ment that  amauroses  have  been  observed, 
1  See  Secondary  Effects,  p.  172. 
125 


THE  THERAPY  OF  SYPHILIS 

and  not  after  only  a  single  larger  dose. 
Syphilitic  diseases  of  the  eyes  without 
participation  of  the  optic  nerves  can 
naturally  be  subjected  without  hesitation 
to  treatment  with  arsenobenzol,  as  is 
evident  from  what  has  been  stated  in 
the  foregoing  pages. 

(/)    SYPHILIS   OF  THE   INTERNAL  ORGANS. 

Very  good  curative  effects  are  often  ob- 
tained in  specific  diseases  of  the  internal 
organs,  which  fall  into  t'ais  period.  Thus, 
F.  Lesser  has  recorded  the  case  of  a  patient 
with  severe  pulmonary  syphilis,  who  was 
treated  and  cured  with  the  Ehrlich  prepara- 
tion. Simultaneously,  L.  Michaelis  stated 
that  he  had  been  able  to  observe  distinct 
improvement,  both  in  chronic  amyloid  as 
well  as  in  acute  syphilitic  forms  of  nephritis, 
when  treated  with  arsenobenzol.  In  two 
cases  of  syphilis  with  nephritis,  Scholtz  saw 
recovery  in  one  case  and  distinct  improve- 
ment in  the  other. 

126 


THE  CHEMOTHERAPY  OF  SYPHILIS 

According  to  the  observations  of  Alt, 
Weber,  and  others,  as  I  have  already  men- 
tioned, cerebral  syphilis  forms  a  very 
gratifying  and  convincing  object  for  treat- 
ment with  arsenobenzol. 

Meirowsky  reports  a  favourable  influence 
on  syphilitic  nephritis,  which,  however, 
was  not  permanent.  As  Wolters  recorded, 
a  case  of  incipient  diabetes  on  a  specific 
basis  was  also  favourably  influenced.  Ac- 
cording to  Duhot,  gummatous  internal 
diseases  are  cured  with  the  same  rapidity 
as  tertiary  ulcers.  Geronne  successfully 
treated  a  case  of  specific  disease  of  the 
liver.  Gennerich  observed  that  visceral 
syphilis  of  six  months'  duration  was  free 
from  pain  the  day  following  the  Ehrlich- 
Hata  injection,  whereupon  the  miserable 
condition  improved.  Wechselmann  records 
a  case  of  the  healing  up  of  severe  ulcerous 
syphilis  of  the  rectum ;  icterus  of  long  stand- 
ing disappeared  within  ten  days.  In  one 
case  of  bilateral  labyrinth  deafness,  accord- 
ing to  Grouven   and  Frankel,  an  unmis- 

127 


THE  THERAPY  OF  SYPHILIS 

takably  distinct  improvement  in  hearing 
set  in  at  the  end  of  twelve  days  after  a 
single  injection  of  0'6  gramme. 


(g)    META-   AND    PARA-SYPHILITIC    DISEASES, 
INCLUDING  TABES   AND   PARALYSIS. 

As  is  known,  the  first  communications, 
with  regard  to  the  therapeutic  efficacy  of 
the    new    Ehrlich    preparation    ''  606 "    in 
nervous  and  mental  diseases  on  a  syphilitic 
basis,   originated   with   Alt.     The  curative 
results   reported,    especially   in   tabes   and 
paralysis,    were    altogether    so    good,    and 
were    stated    so    convincingly,    that    they 
aroused  the  greatest  general  interest.     It 
seemed  as  if,   in  arsenophenylglycin,   and 
more  still  in  arsenobenzol,  an  effective  drug 
had    been  found  '*  which  might  pave  the 
way   for   the   remission   of   paralysis,    and 
provide    a    prophylaxis    for    this    terrible 
disease."     Thus,  for  example,  a  justice  of 
the    peace,    who    had    been    admitted    to 
hospital  on  account  of  progressive  paralysis, 

128 


THE  CHEMOTHERAPY  OF  SYPHILIS 

according  to  the  report  of  Alt  at  the  BerUn 
Medical  Society  (Meeting  of  March  3, 
1910),  had  been  completely  cured  by  a 
single  injection  of  a  relatively  small  dose 
of  arsenobenzol  and  was  again  able  to 
transact  his  business  thoroughly  well.  To- 
day, unfortunately,  we  know  that  it  is 
just  these  syphilitic  nervous  diseases,  and 
especially  the  most  terrible  forms  of  them, 
tabes  and  paral^^sis,  which  are  least  in- 
fluenced by  Ehrlich-Hata  "  606,''  and 
generally  not  at  all.  Proportionately,  even 
Alt  had  soon  to  restrict  his  earlier  opinion 
as  to  the  efficacy  of  arsenobenzol.  He 
stated  that  a  favourable  action  of  this 
drug  was  only  to  be  expected  at  the  begin- 
ning of  tabes  and  of  paralysis — to  a  certain 
extent,  when  the  "  first  lightning  pains  " 
set  in. 

In  the  early  stages  of  so-called  ''tabo- 
paralysis ''  it  appeared  to  Alt  that  treatment 
with  the  new  Ehrlich  preparation  was 
specially  indicated,  and  was  very  efficacious. 
In  the  case  of  those  suffering  from  spinal 

129  I 


THE  THERAPY  OF  SYPHILIS 

paralysis,  Alt's  experience  was  that  in 
the  early  stage  their  chief  trouble  was 
removed  by  such  treatment;  this  was 
demonstrated  chiefly  by  continuous  marked 
diminution  of  their  previous  unbearable 
pain.  Thus,  the  shooting  pains  especially 
were  said  to  cease  at  one  stroke,  Wechsel- 
mann  also  was  able  to  testify  to  a  distinct 
improvement  in  the  sense  of  constriction, 
of  headache,  of  intercostal  neuralgia,  and 
of  weakness  in  the  muscles  of  swallowing 
and  of  the  bladder,  in  patients  suffering 
from  tabes. 

Selley  was  able  to  confirm  the  statements 
of  Alt  to  this  extent — that  he  had  been  able 
to  obtain  a  two-months'  cessation  of  gas- 
tric attacks,  from  which  a  patient  with  tabes 
suffered,  by  treating  him  with  arsenobenzol. 
True,  the  attacks  returned  at  the  end  of 
that  period.  He  saw  an  improvement  of 
dysarthria  in  paralysis. 

Torday  does  not  expect  much  in  ad- 
vanced cases  of  tabes  and  paralysis.  '*  If, 
however,     there    are    manifest    syphilitic 

130 


THE  CHEMOTHERAPY  OF  SYPHILIS 

symptoms  present,  one  can  naturally  ad- 
minister arsenobenzol  as  an  anti-syphilitic 
procedure." 

Favourable  results  were  obtained  in  para- 
lysis to  a  certain  extent  by  Dorr,  Treupel, 
Duhot,  Michaelis,  and  others.  In  treat- 
ing nervous  patients  on  a  specific  basis, 
Friedlander  has  also  observed  a  favourable 
effect  on  existing  pain. 

Gliick  was  twice  unsuccessful  in  advanced 
paralysis,  and  so  was  Geronne  in  twenty 
cases  of  different  syphilitic  sequelae. 
Behring  saw  no  effect  in  six  cases,  and 
Meyer  none  in  sixteen.  Further,  von 
Zeissl  was  unable  to  testify  to  any  specially 
favourable  results  in  similar  diseases. 
Ledermann  had  to  report  failure  in  a 
case  of  facial  paralysis  on  a  specific  basis, 
and  with  a  patient  with  paraplegia  of  both 
legs.  Salmon,  on  the  other  hand,  in  two 
cases  of  hemiplegia  without  contracture, 
was  able  to  testify  to  cure  in  one  case,  and 
at  least  to  distinct  improvement  in  the 
other.     In  his  opinion,  the  drug  is  contra- 

131 


THE  THERAPY  OF  SYPHILIS 

indicated  in  progressive  paralysis.  Schreiber 
saw  marked  improvement  in  a  large  number 
of  epileptic  cases,  which  were  due  to 
syphilis. 

I  will  not  here  go  farther  into  the 
records,  which  for  the  most  part  can  only 
be  regarded  as  problematical,  up  to  the 
present.  We  must  wait  until  reports 
have  come  in  of  extensive  employment  in 
large  psychiatrical  institutions  and  longer 
periods  of  observation  have  elapsed.  I 
should  like,  however,  to  join  issue  with 
Grouven  in  the  opinion  that,  at  the  present 
time,  the  first  ''  lightning  pains ''  of  para- 
syphilitic  diseases  should  not  form  the 
absolute  limit  of  our  therapeutic  treatment 
with  arsenobenzol,  and  that  in  all  cases  of 
tabes  and  paralysis,  where  fresh  symptoms 
are  still  present,  they  should  be  subjected 
to  treatment  with  this  drug  (A.  Neisser). 
True,  the  greatest  caution  is  required  in  all 
diseases  of  the  central  nervous  system, 
and,  according  to  von  Zeissl,  those  cases 
should  be  excluded  in  which   destruction 

132 


THE  CHEMOTHERAPY  OF  SYPHILIS 

has  already  set  in.  As  with  such  patients, 
disturbances  of  the  blood-pressure  and 
of  the  circulatory  apparatus  may  arise 
(Alt,  Schlesinger,  and  others),  Schlesinger 
recommends  that  it  might  be  well  to 
administer  a  cardiac  a  few  days  after  or 
before  the  injection.  ''  Strict  asepsis  is 
important,  five  da3^s'  unconditional  rest 
in  bed,  corresponding  diet,  and  regulation 
of  the  bowels.  It  is  advisable  that  magnesia 
usta  should  be  administered  internally'' 
(von  Zeissl). 

[h)   HEREDITARY  SYPHILIS. 

As  far  as  I  am  aware,  the  first  case  of  con- 
genital syphilis  was  treated  with  arseno_ 
benzol  by  Wechselmann,  who  effected  a 
cure  with  it  in  a  short  time  in  an  infant 
with  a  severe  partly  pemphigoidal  syphi- 
lide.  Two  other  infants  with  pemphigus 
neonatorum  were  also  cured.  Michaehs 
showed  a  child  before  the  Berlin  Medical 
Society,    in  whom,    after   an   injection   of 

133 


THE  THERAPY  OF  SYPHILIS 

o*o6  gramme  of  the  new  Ehrlich  prepara- 
tion, the  symptoms  of  hereditary  syphiHs — 
maculo-papulous  exanthema,  with  infiltra- 
tions on  the  soles  of  the  hands  and  feet — had 
disappeared  within  eight  days.  Only  choryza 
remained  behind.  Recovery  had  com- 
menced on  the  second  day.  Pick  obtained 
a  rapid  curative  effect  in  a  case  of  hereditary 
infantile  syphilis — lues  cutanea  maculosa, 
papulae  frontis,  palmae  et  plantae.  In  the 
Lesser  Chnique  five  infants  with  hereditary 
specific  disease,  with  the  most  varied 
symptoms  (pemphigus  neonatorum.  Par- 
rot's pseudo-paralysis  of  the  arm,  large 
papulous  syphilide,  rhagades  around  the 
mouth,  choryza,  etc.),  recovered  completely 
very  rapidly  after  intragluteal  injections  of 
0*03  to  0*05  gramme  of ''  606.''  According  to 
Spiethoff,  Frankel  and  Grouven,  Pick,  Jun- 
kermann  and  Kalb,  surprising  results  are 
often  obtained  here  with  arsenobenzol  treat- 
ment. Hoffmann  treated  with  0*3  gramme 
a  fifteen-year-old  congenital  syphilitic  youth, 
with    ozaena   syphilitica,    excessive    caries, 

134 


THE  CHEMOTHERAPY  OF  SYPHILIS 

intense  headache,  paralysis  of  the  left 
abducens,  and  protuberance  of  the  bulb. 
The  symptoms  of  the  disease  were  sur- 
prisingly improved ;  the  bulbar  protuber- 
ance and  the  abducens  paralysis  disappeared 
altogether. 

The  Medizinische  Klinik,  on  the  other 
hand,  reports  that,  from  the  private  com- 
munications of  different  teachers,  the 
Ehrlich-Hata  drug  apparently  fails  in  a 
relatively  small  number  of  cases  of  heredi- 
tary syphilis. 

Moreover,  Wechselmann  recommended 
that  only  well-nourished  children  should  be 
subjected  to  the  new  treatment  with  arseno- 
benzol.  ''  Through  the  rapid  liberation  of 
colossal  quantities  of  spirochaetes,  on  the 
administration  of  '  606,'  such  a  number 
of  endotoxines  were  released,  that  a  tem- 
porary injury  was  caused,  which  the  child's 
organism  could  not  stand/' 

Particular  interest  was  aroused  by  a  com- 
munication from  TaegCj  on  the  good  thera- 
peutic result   obtained  in  the   case  of   a 

135 


THE  THERAPY  OF  SYPHILIS 

syphilitic  infant,  by  treating  its  nursing 
mother  with  arsenobenzol.  A  young 
woman,  with  manifest  syphilitic  symptoms, 
had  given  birth  to  a  colourless,  shrivelled, 
old-looking,  apathetic  child,  weighing 
2,400  grammes,  on  July  4,  1910.  On 
July  13,  the  child  developed  pemphigous 
blisters  on  the  soles  of  the  feet  and  parony- 
chia on  the  hands.  On  July  14,  the  mother 
was  given  0*3  gramme  of  arsenobenzol ; 
from  the  third  day  onward  a  surprising 
diminution  of  the  condyloma  and  dis- 
appearance of  the  spirochaetes  was  per- 
ceptible. On  the  same  day  the  syphilitic 
symptoms  of  the  child,  which  up  to  now 
had  increased  in  intensity,  simultaneously 
came  to  a  standstill,  and  then  suddenly  all 
of  them  began  to  recede.  On  the  fifth  day 
the  skin  looked  pink,  the  paron^^chia  had 
disappeared,  and  likewise  the  pemphigus 
up  to  a  small  patch.  On  July  29,  the  child 
weighed  3,900  grammes,  and  exhibited  no 
further  specific  symptoms.  Taege  assumes 
that  antitoxines  had  been  transferred  into 

136 


THE  CHEMOTHERAPY  OF  SYPHILIS 

the  child's  organism  through  the  milk, 
which  had  been  formed  from  the  endo- 
toxines  liberated  in  the  mother's  organism 
from  the  disintegrated  spirochaetes.  Taege 
claims,  therefore,  that  for  s^^philitic  children 
the  syphilitic  mother  should  be  treated 
with  ''  606."  If  she  is  not  able  to  suckle 
her  child  herself,  then  a  syphilitic  wet- 
nurse  should  be  procured,  and  treated  with 
arsenobenzol  before  commencing  her  duty, 
a  demand  which  at  the  present  time  appears 
somewhat  hazardous. 

Duhot  describes  an  analogous  case.  He 
is,  however,  of  opinion  that  an  insufficient 
quantity  of  spirochaetes  are  destroyed  in 
the  child's  organism  by  taking  the  anti- 
infectious  substance  through  the  mother's 
milk.  He,  therefore,  recomm.ends  that  the 
child  itself  shall  also  be  treated  with  ''  606." 
As  Ehrlich  mentions,  similar  cases  have 
been  observed  by  Raubitschek,  Dobrowicz, 
and  others.  Ehrlich  agrees  with  Taege's 
conclusions ;  still  he  advises  that  such 
children  should  have  a  small  dose  of  arseno- 

137 


THE  THERAPY  OF  SYPHILIS 

benzol  injected,  in  order  to  destroy  any 
remaining  spirochsetes. 

Meirowsky  was  able  to  cure  pemphigous 
blisters  in  a  child  with  hereditary  specific 
disease,  by  injecting  serum  taken  from 
syphilitic  patients  who  had  been  treated 
with  "606." 

Similarly,  Marinesco,  Plant,  and  Scholz 
observed  a  favourable  influence  on  syphi- 
litic products,  especially  those  of  congenital 
syphilis,  by  injecting  serum  from  patients 
who  had  been  treated  with  ''  606/'  In  my 
opinion,  it  is  not  yet  clearly  decided  whether 
an  action  of  this  kind,  of  mother^s  milk  and 
serum,  on  patients  treated  with  arsenobenzol, 
should  be  attributed  to  traces  of  arsenic, 
which  might  be  found  in  the  milk  or  blood. 

The  following  case,  described  by  Kalb, 
may  be  given  to  a  certain  extent  in  contra- 
distinction to  those  already  mentioned  :  A 
pregnant  woman,  who  was  suffering  from 
fresh  specific  disease,  was  treated  with  an 
inunction  cure  during  pregnancy  and  with 
calomel  while  suckling.     Despite  this,  the 

138 


THE  CHEMOTHERAPY  OF  SYPHILIS 

child,  although  born  without  syphilitic 
symptoms,  soon  developed  firm  papules  on 
the  face  and  trunk.  Finally,  severe  visceral 
syphilis  set  in,  and  the  child  died. 

Grouven  was  able  to  cure  the  syphilitic 
products  induced  experimentally  in  rabbits, 
by  means  of  serum  from  patients  treated 
with  "  606." 

Von  Zeissl  mentions  that  many  medical 
men  have  had  goats  and  asses  rubbed  with 
mercury,  and  have  then  fed  and  cured 
hereditary  syphilitic  children  with  the  milk 
taken  from  these  mercurialised  animals. 


7.  Dosage. 

With  conceivable  caution,  at  first  only 
small  doses  of  the  Ehrlich-Hata  preparation 
"  606  "  were  administered  for  the  treatment 
of  human  syphilis.  As  Ehrlich  has  reported, 
Truffi  used  only  0*025  "to  o*o5  gramme  in  his 
first  experiments.  The  transition  from  the 
doses  of  0'3  to  0*4  gramme,  v/hich  were 
originally   almost   generally  employed,    to 

139 


THE  THERAPY  OF  SYPHILIS 

higher  ones  has  been  gradual.  According 
to  the  clinical  observations  of  most  authors, 
one  can  go  up  to  from  o*6  to  o*8  gramme  with 
adults,  and  even  to  i*o  to  1*2  gramme, 
especially  with  Ehrlich's  newest  prepara- 
tion ''  hyperideal '  606,' ''  which  is  less  toxic, 
without  causing  any  particular  secondary 
effects.  It  is  only  in  nervous  diseases  that 
Alt  and  Torday  claim,  and  Ehrlich  agrees 
with  them,  that  small  doses  should  be 
retained  (not  exceeding  0*4  gramme),  as 
in  these  cases  one  must  be  very  cautious 
because  of  the  weakness  of  the  whole 
organism  to  the  new  arsenic  preparation. 

Salmon  believes  that  a  smaller  dose  of 
0*3,  0*4,  or  0'5  gramme  will  bring  about 
the  disappearance  of  the  syphilide  just  as 
quickly  as  a  larger  one  of  about  i*o  gramme. 

Schreiber  considers  that  in  intravenous 
injection  one  should  not  exceed  0*4  to 
0-5  gramme.  Weintraub  and  others  inject 
larger  doses,  up  to  07  to  0*8  gramme. 
Iversen  follows  up  the  intravenous  injection 
(on  an  average  with  a  dose  of  0*5  gramme) 

140 


THE  CHEMOTHERAPY  OF  SYPHILIS 

two  or  three  days  later  with  an  intra- 
muscular one,  until  altogether  a  total  of 
0*8  to  1*0  gramme  has  been  injected. 

Ehrlich  considers  that  at  the  present  time  it 
is  impossible  to  give  any  general  figures  with 
regard  to  the  height  of  the  dose ;  in  his  opinion 
this  depends  upon  the  quality  of  the  disease. 

8.  Influencing  the  Result  of  the 
Wassermann  Reaction  by  Means 
OF  Treatment  with  Arsenobenzol. 

According  to  the  first  communications  of 
Wechselmann  and  Lange,  if  the  observation 
period  were  sufficiently  long  the  Wassermann 
reaction,  which  before  the  injection  was 
positive,  would  be  negatived  in  lOO  per  cent, 
of  the  specific  cases  treated  with  an  injection 
of  the  Ehrlich-Hata  preparation.  The  time 
at  which  the  negative  result  set  in  appeared 
to  be  dependent  on  the  preliminary  strength 
of  the  reaction  before  the  injection.  The 
strength  of  the  reaction  itself  should  fall 
into    a   proportionate   curve   without   any 

141 


THE  THERAPY  OF  SYPHILIS 

greater  irregular  variations.  Weber,  Gen- 
nerich,  von  Zeissl,  Pick,  and  McDonagh  also 
confirmed  the  fact  that  in  loo  per  cent,  of 
the  cases  the  previously  positive  reaction 
was  changed  into  a  negative  one.  Accord- 
ing to  Gennerich,  the  appearance  of  the 
negative  reaction  was  accelerated  by  a 
subsequent  second  injection  of  ''606.'' 
Similar  results  were  obtained  by  Hoppe 
and  Schreiber ;  they  got  a  negative  re- 
action in  84*6  per  cent,  of  all  their  cases  ; 
in  a  later  report,  however,  Schreiber  gave 
this  as  only  50  per  cent.  Iversen  considers 
that  the  positive  Wassermann  reaction  dis- 
appears twenty  to  forty  days  after  the 
injection,  and  in  some  cases  even  on  the 
eighth  to  tenth  day.  In  none  of  the  cases 
treated  by  Iversen,  in  which  the  reaction 
became  negative,  did  the  result  again 
become  positive.  It  happened  in  a  few 
cases  that,  soon  after  the  injection  of 
arsenobenzol,  the  intensity  of  the  Wasser- 
mann reaction  increased,  to  again  slowly 
diminish    later.      The    same    phenomenon 

142 


THE  CHEMOTHERAPY  OF  SYPHILIS 

was  observed  by  Grouven  and  Michaelis. 
Spiethoff  considers  that  with  this  treatment 
the  Wassermann  reaction  becomes  negative 
after  four,  six,  or  eight  weeks.  ''  In  many 
cases  the  reaction  gradually  ceased,  and 
in  others  variations  set  in  before  the 
permanent  negative  phase."  Frankel  and 
Grouven  were  able  to  testify  to  a  negative 
result  of  the  Wassermann  reaction  three 
weeks  after  the  injection  of  a  large  number 
of  tabetic  and  paralytic  patients.  In  the 
other  cases,  a  very  considerable  change  of 
the  conditions  became  evident  in  the  form 
of  a  marked  weakening  of  the  reaction. 
With  specific  patients,  on  the  other  hand, 
although  it  is  true  these  authors  often  saw 
the  reaction  distinctly  influenced,  ''fre- 
quently, despite  noticeable  cHnical  improve- 
ment, the  sero-diagnostic  result  remained 
unvaryingly  positive." 

Alt  also  found  that  there  was  a  negative 
reaction  in  a  distinctly  higher  percentage 
of  paralytics  than  there  was  of  syphilitic 
patients.     In  Herxheimer's  experience,  the 

143 


THE  THERAPY  OF  SYPHILIS 

reaction  still  remains  positive  in  many 
cases,  but  in  three-quarter  of  those  which 
were  observed  constantly  it  was  negative 
at  the  end  of  fifty  days.  Linser  obtained 
a  negative  reaction  in  about  60  to  70 
per  cent,  of  the  cases,  while  Kromayer  and 
Stern  only  got  one  in  50  per  cent. 

According  to  Bering,  an  occasional  change 
of  the  reaction  sets  in  after  four  to  five 
weeks ;  in  forty  cases  the  Wassermann 
reaction  did  not  alter,  while  in  twenty-six 
it  swung  back  from  a  positive  to  a  negative 
result.  Geronne  likewise  was  only  able  to 
obtain  a  negative  reaction  in  thirty-seven 
out  of  seventy-seven  patients.  A  second 
injection  rendered  nine  more  cases  negative. 
A.  Neisser  was  at  first  only  able  to  prove  a 
negative  reaction  in  about  10  per  cent.,  and 
later  in  44  per  cent.,  of  cases  after  treatment 
with  arsenobenzol.  This  occurred  only  in 
those  patients  who  came  under  treatment 
very  early  after  infection  and  after  the 
appearance  of  the  primary  affection.  Gliick 
only  saw  a  subsequent  negative  reaction  in 

144 


THE  CHEMOTHERAPY  OF  SYPHILIS 

five  out  of  twenty  cases  treated.  Schlesinger 
found  the  Wassermann  reaction  after  two 
to  ten  weeks ;  Miekley,  generally  positive 
after  more  than  two  months  ;  Scholtz  also 
considered  that  the  reaction  was  still  posi- 
tive five  to  six  weeks  after  the  injection. 
Similar  results  were  arrived  at  by  Loeb, 
Isaac,  Hermann,  Brandle,  and  Clingestein, 
Anscherlik,  Pick,  Halberstadter,  Bruhns, 
Torday,  and  others. 

In  my  cases  also  the  Wassermann  reaction 
was  only  negative  once. 

With  regard  to  the  result  of  the  Wasser- 
mann reaction  in  hereditary  syphilitic  in- 
fants and  children,  the  same  conditions 
seemed  to  apply  to  those  which  exist  in  the 
case  of  children  treated  with  mercury — 
namely,  a  very  rare  negative  reaction.  As 
is  known,  various  authors,  including 
Michaelis  and  I  myself,  have  proved  that  in 
the  case  of  hereditary  syphilitic  children,  it 
is  very  difficult  to  change  the  positive  re- 
action into  a  negative  one  by  means  of 
mercury. 

145  K 


THE  THERAPY  OF  SYPHILIS 

As  is  evident  from  the  foregoing  summary 
of  the  authors'  results,  apparently  the 
Wassermann  reaction  remains  positive  in  a 
fairly  large  percentage  of  cases  after  treat- 
ment with  arsenobenzol.  True,  the  majority 
of  these  results  refer  to  a  single  treatment, 
often  only  with  small  doses.  It  is  not 
possible  at  present  to  decide  definitely 
whether,  with  larger  doses  and  occasionally 
with  repeated  arsenobenzol  injections,  or 
with  intravenous  application,  this  reaction 
would  be  negative  in  all  cases,  and  remain 
so  permanently  (Gennerich).  Ehrlich  con- 
siders the  behaviour  of  the  Wassermann 
reaction  of  the  greatest  importance  in 
estimating  *'  606 ''  treatment.  He  says 
that  every  case  in  which  the  reaction  per- 
sists after  treatment  must  be  taken  as 
uncured.  A  negative  reaction,  if  it  remains 
lastingly  negative,  may  be  regarded  as 
indicative  of  cure.  It  is,  however,  possible 
that  it  is  only  a  negative  phase,  if  the  reac- 
tion subsequently  again  becomes  positive. 
In   that   case,    according   to   Ehrlich,    the 

146 


THE  CHEMOTHERAPY  OF  SYPHILIS 

injection  only  diminished  the  number  of 
spirochaetes  in  the  organism.  The  re- 
mainder were  no  longer  capable  of  inciting 
a  positive  reaction.  But  if  these  had  again 
increased,  then  the  result  would  again 
become  positive.  Ehrlich,  therefore,  re- 
gards a  renewal  of  the  positive  Wasserman 
reaction  as  analogous  to  a  relapse  without 
external  symptoms,  and  hence  as  an  indi- 
cation to  repeat  the  injection.  Taking  this 
into  consideration,  Ehrlich  claims  that  it 
will  be  possible  to  control  the  treatment 
within  certain  periods,  by  examining  the 
blood  with  the  Wassermann  test.  Now, 
however,  even  with  the  Ehrlich-Hata  treat- 
ment, various  teachers  have  observed  that, 
despite  the  existence  of  florid  specific 
symptoms,  it  is  possible  for  the  result  of 
the  reaction  to  be  negative.  Volk  and 
Lipschiitz  assert  that  in  one  of  their  cases 
which  relapsed,  the  reaction  was  con- 
tinuously negative.  Therefore,  too  much 
importance  must  not  be  laid  on  a  negative 
result  of  the  Wassermann  test.     In  mer- 

147 


THE  THERAPY  OF  SYPHILIS 

curial  treatment,  I  have  detected  repeated 
backward  and  forward  fluctuation  of  the 
reaction  from  a  positive  to  a  negative  result, 
and  vice  versa  during  treatment.  In  order 
to  obtain  a  certain  and  constant  result  as 
far  as  possible,  the  blood  should  not  be 
tested  during  or  immediately  after  finishing 
the  mercurial  cure,  but  one  should  wait 
until  some  little  time  after  treatment- 
Similarly,  the  blood  should  not  be  examined 
immediately  after  the  injection,  for  one 
might  be  deceived  by  the  arise  of  a  so- 
called  ''  negative  phase,"  when  forming  an 
opinion  as  to  the  influence  of  the  treatment 
on  the  result  of  the  reaction. 

The  phenomenon  observed  on  various 
sides  (Wechselmann,  Neisser,  Iversen,  and 
others),  that  in  many  cases  a  reaction  which 
was  originally  negative  became  positive 
after  the  injection,  is  explained  by  Ehrlich 
by  the  fact  that  the  spirochaetes  present 
before  treatment  were  not  sufficient  to 
incite  a  positive  reaction.  These  spiro- 
chaetes,   however,    were   liberated   by   the 

148 


THE  CHEMOTHERAPY  OF  SYPHILIS 

injection  of  arsenobenzol,  and  their  endo- 
toxines  freed.  These  became  absorbed,  and 
thus  brought  about  a  positive  result.  Citron 
considers  that  this  phenomenon  is  simply 
due  to  the  fact  that  the  examination,  and 
injection  respectively,  were  undertaken 
shortly  before  the  reaction  had  become 
positive.  If  one  had  only  waited  a  short 
time,  then  the  reaction  would  have  become 
positive  without  an  injection. 


9.  Relapses. 

Wechselmann  stated,  in  March,  1910, 
that  he  received  the  new  preparation  *'  606  '' 
from  Privy  Councillor  Ehrlich,  and  had  not 
been  able  to  discover  any  relapse  within 
three  months  in  the  hundreds  of  cases  he 
had  treated  up  to  then.  Meanwhile,  he  had 
passed  on  from  the  original  dose  of  0*3  to  0*45 
gramme  for  women,  and  0*5  gramme  for  men. 
In  a  later  report,  August  11,  1910,  on  his 
503  cases  of  disease  treated  with  dioxydi- 

149 


THE  THERAPY  OF  SYPHILIS 

amidoarsenobenzol,  Wechselmann  recorded 
three  relapses ;  certainly  only  a  very  small 
portion  of  the  cases  treated  had  come  to  see 
him  again.  In  the  meanwhile,  however, 
reports  of  various  recurrences  had  come  to 
hand  from  other  sides  after  a  preliminary 
injection  of  arsenobenzol.  Thus,  at  a  dis- 
cussion held  at  the  Gottinger  Medical 
Society,  on  June  2,  Schreiber  and  Hoppe 
stated  they  had  seen  relapses,  and  the 
reappearance  of  fresh  specific  efflorescences 
respectively,  in  ten  cases  within  four  weeks 
after  0*3  to  0*4  gramme  of  arsenobenzol. 
A.  Neisser  also  reported  various  recurrences 
on  June  30,  19 10.  He  attributed  these  to 
the  fact  that  the  doses  administered  had 
been  too  small — viz.,  0*4  gramme.  Geronne 
and  Huggenberg  recorded  that  after  obser- 
vations extending  over  thirteen  weeks  they 
could  testify  to  five  relapses,  amongst  others 
*'  three  men  we  had  treated  intramuscu- 
larly and  intravenously  respectively  for 
primary  ulcer.  Here  the  clinical  phe- 
nomena    first     disappeared     surprisingly 

159 


THE  CHEMOTHERAPY  OF  SYPHILIS 

rapidly,  the  Wassermann  reaction  became 
negative  soon  after  the  injection,  and  re- 
mained so  for  several  weeks,  and  then, 
after  seven  to  eight  weeks,  in  place  of  the 
primary  ulcer,  a  fresh  erosion  was  formed, 
in  which  spirochaetes  could  be  detected. 
In  these  cases  the  Wassermann  test  had 
again  become  positive/' 

Hoffmann  recorded  relapses  after  an 
injection  of  the  Ehrlich  drug,  and  mentions 
that  it  is  not  uncommon  to  prove  the 
presence  of  spirochaetes  in  these  relapses  at 
a  time  when  the  Wassermann  reaction  is 
still  perfectly  negative. 

On  August  4,  1910,  BohaC  and  Sobotka 
reported  four  relapses  they  had  observed 
within  a  few  weeks  ;  0*3  gramme  had  been 
injected.  Neisser  and  Kusnitzki  saw  alto- 
gether five  relapses,  which  they  attributed 
to  the  fact  that  the  doses  administered  had 
been  too  small.  Loeb  observed  a  recur 
rence,  certainly  after  the  application  of  a 
very  small  intravenous  dose  of  0*14  gramme. 
Ehrlich    stated,    in    a    communication    on 

151 


THE  THERAPY  OF  SYPHILIS 

August  12,  1910,  that  up  to  that  day  there 
had  been  about  4,000  cases  under  careful 
observation.  He  declared  that  in  man 
complete  recovery  was  possible  with  the 
new  drug  in  90  per  cent,  of  the  cases.  This 
calculation  was  probably  made,  in  con- 
sideration of  the  fact  that  up  to  that  time 
there  were  only  a  small  number  of  cases  in 
which  the  clinical  symptoms  of  specific 
disease  had  recurred. 

According  to  a  still  later  communication 
of  Wechselmann's,  the  number  of  relapses, 
and  partial   failures   respectively,   out   of 
the  900  cases  he  had  treated  up  to  the 
time  of  publication  was  small,  almost  down 
to   vanishing-point;    at    any    rate,    ''the 
number  of  the  earlier  recurrences  remained 
far  behind  those  of  mercurial  treatment.'' 
Wechselmann  specially  emphasises  the  in- 
significance   of    the    relapses.     Kromayer, 
Brandle,   and  Clingestein,   out  of  twenty- 
seven  cases,  saw  five  relapses  after  two  and 
a  half  to  three  weeks.     Gliick  and  Wolff 
observed    four    recurrences.      Fischer    re- 

152 


THE  CHEMOTHERAPY  OF  SYPHILIS 

ported  two  severe  relapses  in  patients 
treated  by  others  with  ''  EhrHch-Hata/'  and 
in  one  extensive  primary  affection  contain- 
ing spirilla,  which  had  been  injected  about 
eight  weeks  previously.  Duhot  saw  a  relapse 
in  a  patient  who  had  been  treated  by  another 
medical  man  with  0*3  gramme.  Geronne 
saw  fourteen  relapses  in  about  eighty  syphi- 
litic patients,  who  had  been  at  least  ten 
to  twelve  weeks  under  careful  observation  ; 
he  did  not  include  in  this  summary  the 
numerous  patients  who  had  been  under 
observation  for  a  shorter  time.  Eleven 
times  there  were  reindurations  of  the 
primary  affection,  renewed  appearance  of  a 
specific  angina  or  of  an  exanthem ;  three 
patients  got  other  similar  specific  symptoms. 
Denecke  testified  to  the  certain  recurrence 
of  an  early  tertiary  ulcerous  process. 
Ledermann,  up  to  date,  records  a  return 
of  periostitic  swelling  of  the  cranium,  which 
had  completely  disappeared  with  its  symp- 
toms, after  an  injection  of  0*45  gramme ;  the 
appearance  of  roseola  fourteen  days  after 

153 


THE  THERAPY  OF  SYPHILIS 

involution  of  the  primary  affection  (with 
0'3  gramme),  and  two  other  relapses. 
Rille  saw  a  recurrence  of  the  primary- 
affection  about  four  weeks  after  cure. 
Weber  observed  two  slight  relapses,  and 
Gennerich  four  in  malignant  syphilis  after 
almost  four  weeks.  In  a  recent  com- 
munication, Schreiber  put  the  total  number 
of  his  relapses  at  sixteen  after  0*3  and 
0*4  gramme  respectively ;  one  recurrence 
after  0*7  gramme  ;  he  had  no  relapses  after 
intravenous  injection.  Herxheimer  also, 
in  his  last  report  of  230  cases,  mentions 
two  very  slight  local  returns  of  secondary 
syphilis  within  four  and  a  half  months. 

Linser,  on  the  other  hand,  repeatedly 
noticed  relapses  in  all  stages,  some  of  which 
occurred  within  four  to  six  weeks  of  the 
injection.  In  Bering's  observations,  three 
recurrences  of  secondary  syphilis  appeared 
in  his  cases  at  the  end  of  three  to  four  weeks, 
despite  the  fact  that  the  normal  dose  had 
been  injected.  In  tertiary  syphilis  he  regis- 
tered a  relapse  at  the  end  of  four  weeks. 

154 


THE  CHEMOTHERAPY  OF  SYPHILIS 

Stern  reported  that  in  one  of  his  cases  of 
primary  affection,  with  extensive  exanthem, 
which  had  healed  up  by  eighteen  days  after 
the   appHcation  of   ''  606/'   the  exanthem 
having  gradually  retrogressed,  there  was  a 
return  of  the  papules  on  the  thigh  and  of 
the  mucous  papules  on  the  tongue  and  lip. 
Miekley  observed  two  cases  of  relapse.     In 
three  cases  of  primary  affection,  Grouven 
was  unable  to  prevent  the  appearance  of 
the  secondary  phenomena,  despite  injections 
of  0*3,  0-4,  and  0*5  gramme.    He  saw  direct 
recurrences  in  a  case  of  congenital  syphilis 
(0-05  gramme),  and  in  one  of  acquired  specific 
disease  (after  o"  3  and  0*6  gramme) .    Accord- 
ing to  Friedlander,  an  injection  of  "  Ehrlich- 
Hata''  did  not  prevent  the  appearance  of 
later  secondary  phenomena  in  three  cases 
of   primary  affection.     Joseph  records  one 
relapse  after  0*3  gramme  ;   Eitner  two.     I 
myself    have    had    four    certain    relapses 
and  two  partial  failures  in  the  relatively 
small   number    of    cases    (twelve)    I    have 
treated  with   ''606"    (on  an  average,  o-6 

155 


THE  THERAPY  OF  SYPHILIS 

gramme,  partly  in  alkaline  solution,  partly 
in    neutral   calcium   carbonate    emulsion). 
In  one  of  the  cases  which  recurred  after  the 
prompt    and   rapid   healing    of   two    firm 
papules  in  both  naso-labial  folds,  and  in 
both  angles  of  the  mouth  after  0*45  gramme 
of  arsenobenzol,  a  new  papule  appeared  at 
the  left  angle  of  the  mouth,  about  fourteen 
days   later,    small   plaques   in   the   buccal 
mucous  membrane,  and  a  slightly  indurated 
ulcer,   covered  with   slime,    in  the  sulcus 
coronarius.     In  the  second  case,  a  maculo- 
pustulous  exanthem  healed  up  completely 
within   eight   days.     Fourteen   days   later 
this  exanthem  reappeared  in  an  exaggerated 
form  ;  there  was  also  an  extensive  impetig- 
inous syphilide  at  the  back  of  the  head. 
These  phenomena  then  disappeared  com- 
pletely  after   two   to   three   injections   of 
thymol  acetin.     With  one  patient,  who  had 
a  hard  infiltrated  primary  affection  localised 
in  a  urinary  fistula,  and  marked  bilateral 
typical  swelling  of    the  lymphatic   glands 
with  large   quantities   of   spirochaetes  and 

156 


THE  CHEMOTHERAPY  OF  SYPHILIS 

isolated  roseola,  a  distinct  Herxheimer 
reaction  set  in  on  the  day  following  the 
injection,  which  disappeared  at  the  end  of 
forty-eight  hours.  The  infiltration  of  the 
primary  affection  had  partially  disappeared, 
as  well  as  half  of  the  left  inguinal  gland. 
Ten  days  after  the  injection,  there  was  a 
sudden  outbreak  of  numerous  slightly  in- 
filtrated roseolce  on  the  upper  part  of  the 
body  and  on  the  face.  Finally,  in  the 
fourth  case,  one  of  latent  specific  disease 
with  positive  Wassermann  reaction,  papules 
appeared  on  the  palmar  eminences  and  on. 
the  arms  four  weeks  after  the  injection  of 
arsenobenzol.  Urticarial  roseola,  with  posi- 
tive spirochaete  result  in  some  of  the  roseolae, 
only  healed  partly  ;  sHghtly  infiltrated  and 
pigmented  places  still  persisted.  In  one 
case  the  primary  affection  only  healed  up 
imperfectly,  and  a  severe  eruption  of  roseola 
soon  appeared. 

Apart  from  these  certain  relapses,  how- 
ever, there  are  a  large  number  of  other 
observations    in    which    only    a    defective 


THE  THERAPY  OF  SYPHILIS 

action  of  the  arsenobenzol  on  the  syphilitic 
process  could  be  proved. 

In  current  literature  such  ''  failures  "  are 
generally  recorded  apart  from  the  relapses, 
although  the  latter,  in  the  opinion  of  Stern, 
must  also  be  counted  as  ''  failures,*'  and  in 
this  I  thoroughly  agree  with  him. 

Wechselmann  especially  reports  a  whole 
number  of  such  cases  in  his  last  publication, 
"  The  Reinjection  of  Dioxydiamidoarseno- 
benzol,"  in  which  a  single  injection  of 
''  Ehrlich-Hata  "  did  not  act  as  promptly  and 
perfectly  as  Wechselmann  had  regularly 
observed  previously.  Thus,  amongst  others, 
infants  suffering  from  pemphigus  neona- 
torum, cases  of  severe  malignant  syphilis, 
which,  it  is  true,  were  influenced  in  the  most 
brilliant  manner,  but  which  still  showed 
quite  small  ulcerations,  and,  further,  an 
extensive  papulous  syphilide  and  a  large 
flaked  urticarial  roseola,  were  all  reinjected. 
In  Wechselmann's  experience,  however,  the 
number  of  partial  failures,  as  contrasted 
with  the  number  of  prompt  effects,  is  still 

158 


THE  CHEMOTHERAPY  OF  SYPHILIS 

SO  small  as  to  be  almost  at  vanishing-point. 
Grouven  and  Frankel  were  able  to  observe 
that  sometimes  the  success  of  the  treatment 
appeared  much  less  rapidly.  '*  In  a  facial 
papule  two  months  after  the  first  injection, 
a  large  number  of  mobile  spirochaetes  were 
found.  Another  patient  required  three 
injections,  extending  over  two  months,  to 
effect  the  disappearance  of  his  tubero- 
serpiginous  phenomena."  Treupel  observed 
a  similar  failure  in  a  papule  of  the  lower  lip, 
which,  it  is  true,  reacted  with  redness  and 
moisture,  but  did  not  become  smaller. 
Gliick  saw  thick  papules  and  a  primary 
affection  uninfluenced  at  the  end  of  three 
weeks.  Hartung  also  did  not  always  obtain 
satisfactory  results  in  anal  and  genital 
papules.  Iversen  was  unable  to  effect  the 
cure  of  large  papules  within  three  weeks; 
Hoffmann  found  the  action  inadequate  for 
an  intense  papulous  syphilide,  and  had  to 
supplement  it  by  inunction  treatment. 

Pinkus    stated   that    in   two    cases    the 
secondary  syphilitic  papulous  exanthem  had 

159 


THE  THERAPY  OF  SYPHILIS 

not  disappeared  at  the  end  of  four  weeks 
(with  0'4  and  0*45  gramme)  ;  moreover, 
Spiethoff  also  records  failures  with  these 
doses.  Out  of  sixty-four  cases  of  secondary 
syphilis,  Bering  five  times  saw  the  symptoms 
uninfluenced,  although  in  some  cases  very 
high  doses  had  been  administered  (o*  8  gramme 
per  kilogramme  of  the  weight  of  the  body). 
Scholtz  recorded  three  failures  with  smaller 
doses  of  0*3  to  0*4  gramme ;  in  two  cases  of 
malignant  syphilis,  Geronne  found  that  after 
0*3  and  o*6  gramme,  not  only  was  there  no 
cure,  but  a  week  later  he  discerned  distinct 
deterioration.  Here  belongs  also  the  case 
mentioned  by  W.  Fischer  of  considerable 
exacerbation  of  tertiary  ulcerous  syphilis 
after  an  arsenobenzol  injection.  In  eight 
cases,  out  of  eighty  treated  with  Ehrlich's 
'*  606 ''  up  to  September  15,  1910,  Stern 
could  not  speak  of  a  noticeable  rapid  result, 
neither  could  Taege  in  the  cases  of  a  man 
with  papules  in  his  beard  and  of  a  woman 
with  tumour  of  the  liver.  Volk  and  Lipschiitz 
also  saw  two  cases  of  atonic  ulcers,  which 

160 


THE  CHEMOTHERAPY  OF  SYPHILIS 

were  absolutely  uninfluenced.  Eitner  also 
records  four  failures. 

Quite  recently  the  Medizinische  Klinik 
started  a  fresh  inquiry,  in  which  the  par- 
ticipators in  the  earlier  one  were  asked  to 
make  additions  to  their  contributions,  with 
regard  to  the  number  of  cases  treated.  I 
will  here  briefly  recapitulate  the  contents  of 
this  inquiry,  in  order  to  complete  and  extend 
the  report  of  the  relapses  and  failures  up  to 
the  present  time,  as  far  as  possible. 

Jadassohn  treated  eighty  cases  up  to 
October  24.  The  relapse  of  one  patient 
with  plaques  muqueuses  was  reported  six 
weeks  after  he  had  had  an  injection  of 
0"5  gramme.  A  second  patient  was  given 
0*6  gramme  arsenobenzol,  and  plaques  were 
again  evident  five  weeks  later.  In  a  third 
case,  new  papulous  deposits  appeared 
only  twelve  days  after  the  injection  of 
0-6  gramme.  Out  of  789  cases,  Herxheimer 
saw  33  relapses,  Linser  4  out  of  80.  Spiethoff 
states  that  the  number  of  cases  he  has 
treated  amounts  to  175  ;  amongst  them  there 

161  L 


THE  THERAPY  OF  SYPHILIS 

were  5  recurrences,  2  of  which  were  observed 
after  a  second  injection.  Bering  was  able 
to  make  a  later  examination  of  211  cases ; 
amongst  these  he  observed  25  failures,  which 
equals  11 '8  per  cent.  Pinkus,  120  cases, 
3  relapses ;  Rille,  171  cases,  7  relapses ; 
Treupel,  120  cases,  4  relapses  ;  Juliusberg, 
55  cases,  and  2  recurrences  and  failures 
respectively.  Grouven  treated  altogether 
254  cases  with  arsenobenzol ;  15  of  these 
were  failures  in  the  sense  that  the  symptoms 
only  retrogressed  lingeringly  or  imperfectly : 
9  cases  relapsed.  Bettmann  observed  8 
relapses  amongst  the  cases  he  had  treated 
previously  (87).  Schultz,  i  recurrence 
out  of  28  cases ;  McDonagh,  2  relapses 
out  of  85  cases  ;  Wechselmann,  40  out  of 
1,250  cases.  ''  But  the  number  is  quite 
insignificant,  as  only  a  moderate  percentage 
of  those  treated  again  presented  them- 
selves "  (Wechselmann). 

Amongst  120  cases  of  pure  syphilis 
(not  parasyphilitic  diseases),  L.  Michaelis 
observed   4  relapses ;    up   to   the   present 

162 


THE  CHEMOTHERAPY  OF  SYPHILIS 

Kromayer  has  treated  310  patients,  and  7 
of    these    relapsed.     "  I    may    add/'    says 
Kromayer,  ''  that  the  majority  of  the  cases 
treated  have  not  entered  upon  the  stage 
when  a  recurrence  may  be  anticipated,  so 
that   the   numbers   310   and   7   cannot   be 
placed    in    relation    to    each    other/'      E. 
Saalfeld  saw  5  relapses  out  of  36  cases  ; 
Halberstadter  6  out  of  55  ;  Ledermann  also 
6  out  of  52  ;  Chrzelitzer  only  i  recurrence 
out  of  47  cases.     Gennerich  was  able  to 
treat  82  cases  ;  in  4  of  malignant  syphilis 
he  had  relapses  at  first,  but  later,  in  these 
cases  also,  by  the  aid  of  renewed  injections, 
he  was  able  to  effect  cures.     Scholtz  dis- 
covered 5  relapses  out  of  130  cases  treated  ; 
Schreiber  had   18  recurrences  out  of   152 
cases  which  had  been  subjected  to  intra- 
muscular  injections,    but   there   was   only 
I  relapse  amongst  565  cases  treated  intra- 
venously.    Geronne  reports  that  out  of  71 
patients   with   specific   disease,    who   were 
injected  between  the  months  of  April  and 
June,    22    clinical    recurrences    had    been 

163 


THE  THERAPY  OF  SYPHILIS 

observed  up  to  the  present  date ;  *'  24  of 
these  patients  were  reinjected,  on  account 
of  the  persistence  of  the  Wassermann  re- 
action, by  means  of  which  the  appearance 
of  further  chnical  relapses  was  obviously 
prevented/'  Since  the  middle  of  August, 
Bruhns  has  treated  74  cases  with  EhrHch- 
Hata  '*  606  "  ;  up  to  now  he  has  seen  5 
relapses  and  4  failures.  Welander  treated 
65  cases  altogether ;  but  in  his  opinion  this 
number  also  is  without  importance  in 
estimating  the  relapses.  The  result  of  his 
arsenobenzol  treatment  is  better  indicated 
by  the  fact  that,  of  his  46  adult  patients,  in 
all  probability  no  relapse  occurred  in  27 
cases.  Welander  also  received  notifications 
of  the  relapse  of  11  adult  patients ;  in  5 
cases  the  symptoms  were  but  little  in- 
fluenced. A  recurrence  was  observed  in  the 
case  of  a  child  (hereditary  syphilis),  and 
with  another  the  treatment  failed.  Von 
Zeissl  saw  4  relapses  out  of  149  cases. 
Finally,  Dreuw  was  able  to  observe  4  severe 
relapses  amongst  the  cases  of  11  prostitutes 

164 


THE  CHEMOTHERAPY  OF  SYPHILIS 

subjected  to  police  inspection,  who  had 
been  treated  elsewhere  by  Ehrlich-Hata 
injections.  Polland  and  Knaur  saw  4  recur- 
rences in  the  secondary  stage,  and  in  one 
case  an  Ehrlich-Hata  injection  had  not  the 
slightest  effect.  Latterly,  Wechselmann  has 
observed  severe  eye  trouble  as  a  relapse. 

Cohn  has  also  reported  an  iritis  relapse, 
which  reappeared  fourteen  days  after  a 
prompt  cure  had  been  effected  with  ''606.''  A 
probable  specific  neuritis  of  the  optic  nerve 
was  seen  by  Kowalewski,  in  a  secondary 
syphilitic  woman,  about  two  months  after 
an  Ehrlich-Hata  injection.  Fischer  also 
testified  to  5  severe  cases  of  eye  diseases 
out  of  8  certain  relapses. 

Fischer  is  inclined  to  connect  this 
form  of  relapse  with  the  arsenobenzol 
treatment.  He,  like  Buschke,  believes  the 
neurotropic  affinity  of  this  drug  to  a  certain 
extent  produces  a  locus  minoris  resistentice, 
on  which  the  syphilitic  virus  fastens  itself 
and  finds  a  favourable  field  for  development. 

Wechselmann,    who,    as   we   have   seen, 

165 


THE  THERAPY  OF  SYPHILIS 

only  observed  the  very  slightest  clinical 
relapses,  believes  that  these  "  are  only  to  be 
regarded  as  relapses  of  encapsulated  foci, 
which  have  been  made  manifest  under  the 
action  of  the  drug/'  *'  Our  conception  is 
that  all  the  spirochsetes  which  come  in 
contact  with  the  drug  are  destroyed,  and 
probably  softening  processes  take  place  at 
the  infiltration  foci,  which  harbour  encapsu- 
lated spirochaetes,  and  thus  may  make  them 
accessible  to  the  new  drug."  Wechselmann 
believes  that  the  dose  of  0*5  to  0*6  gramme 
for  men,  and  0*45  gramme  for  women,  which 
has  been  found  effective  and  generally  ade- 
quate for  cure,  should  not  be  exceeded. 

In  the  circular  letter  of  October  25,  1910, 
already  referred  to,  Ehrlich  attributes  the 
appearance  of  relapses  to  the  fact  that 
the  subcutaneous  injection  of  neutral  emul- 
sions accomplishes  less  quoad  duration  of 
effect  than  other  forms  of  application.  It 
seems  to  him  as  though  the  ictus  immuniso- 
toricus  in  this  method  is  not  intense  enough 
to  generally  obtain  a   destruction  of  the 

166 


THE  CHEMOTHERAPY  OF  SYPHILIS 

spirochsetes  to  the  extent  of  sterilisation. 
As  is  known,  it  is  for  this  reason  that 
EhrHch  now  hopes  to  be  able  to  anticipate 
better  results  from  the  treatment  with 
intravenous  injections. 

If,  as  is  assumed  by  Ehrlich  and  a  large 
number  of  syphilidologists,  the  positive  or 
repeated  negative  result  of  the  Wassermann 
reaction  is  a  sure  test  as  to  whether  the 
syphilis  is  healed  up  or  not,  then  naturally 
amongst  these  clinical  relapses  and  failures 
a  large  number  of  cases  must  also  be 
reckoned,  in  which  through  a  single  and 
even  repeated  injection,  the  positive  result 
of  the  sero-reaction  was  not  lastingly  trans- 
formed into  a  negative  one. 

In  estimating  the  number  of  relapses  of 
manifest  specific  symptoms  detected  by 
individual  teachers,  there  are,  in  my 
opinion,  still  some  important  points  to  be 
taken  into  consideration. 

In  the  first  place,  the  statistics  compiled 
by  most  authors  from  which  they  adduce 
and   calculate   the   relapses   are   incorrect. 

167 


THE  THERAPY  OF  SYPHILIS 

As  has  been  claimed  by  Blaschko,  not  only 
must  the  stage  of  the  disease  be  given  accur- 
ately, but  also  how  long  the  affection  has 
been  lying  dormant  in  the  cases  treated. 
But^  above  all,  the  observation  period  is  still 
far  too  short  to  enable  one  to  formulate  any 
definite  conclusions  with  regard  to  the  action 
of  the  arsenobenzol. 

According  to  Alt's  communication,  the 
first  attempts  at  treating  florid  syphilitic 
patients    with     ''  606 "     were    begun    on 
January  31,  1910.     Wechselmann  first  re- 
ceived  this   preparation   from    Ehrlich   in 
March,  1910,  and  most  other  teachers  were 
only  able  to  commence  their  therapeutic 
researches  with  arsenobenzol  much  later. 
Hence  the  longest   observation  period  of 
syphilitic  cases  which  have  been  subjected 
to  this  method  of  treatment,  in  the  most 
favourable  ones,  is  only  a  little  over  nine 
months,  in  many  at  most  half  a  year,  while 
in  most  of  those  cases  reported  up  to  the 
present,    it    is    only   a   few   months.     We 
know,  however,  that  in  the  so-called  early 

168 


THE  CHEMOTHERAPY  OF  SYPHILIS 

treatment    of    syphilis  —  excision    of    the 
primary  affection,  with  subsequent  intense 
mercurial  treatment — with  apparently  com- 
plete cure,  the  appearance  of  recurrences  or 
secondary  symptoms  ma}',  under  some  cir- 
cumstances, be  delayed  for  above  a  year. 
I  myself  have  had  two  observations  of  this 
kind,    which    I    give.     In   one    case,    after 
excision  of  the  primar^^  affection  and  after 
three  intense  injection  cures,  it  was  eight 
months  after  the  excision  that  pronounced 
roseola,  with  impetigo  capitis  and  character- 
istic fall  of  hair,  appeared  (the  Wassermann 
reaction  had  fluctuated    equally  between 
positive  and  negative) .  In  the  other  case,  the 
first  hardly  perceptible  roseola  showed  itself 
about  six  months  after  the  excision  ;  the 
second,  which  was  not  much  more  marked, 
about  three  months  later. 

It  is  evident  from  these  observations  that 
the  course  of  specific  disease  may  deviate 
from_  its  typical  curve,  if  the  development 
of  the  syphilitic  process  is  inhibited  early, 
by  means  of  drastic  cures  or  strong  specific 

169 


THE  THERAPY  OF  SYPHILIS 

drugs.  There  is  no  doubt  that  Ehrlich's 
arsenobenzol  is  a  preparation  which  has  a 
strong  specific  action  on  syphiHtic  infected 
tissues  of  all  kinds.  Consequently,  it  is 
only  possible  to  expect  to  be  able  to 
arrive  at  definite  conclusions  as  to  the 
possibility  of  a  recurrence  of  the  process  of 
disease  after  at  least  twelve  to  eighteen 
months'  careful  observation  of  the  cases 
thus  treated. 

A  further  fact,  which  must  be  taken  into 
consideration,  is  that  perhaps  at  the  begin- 
ning, in  conceivable  enthusiasm  over  the 
good  s^^mptomatic  effect  of  the  new  Ehrlich- 
Hata  preparation,  the  results  of  the  ''  cures'' 
published  were  too  rapid,  and  perhaps  also 
too  euphemistic.  In  the  great  interest 
which  naturally  was  aroused  by  such  publi- 
cations, even  the  smallest  report  was 
referred  to  in  detail  in  the  daily  press.  Thus 
the  public  at  large  got  the  firm  belief  that 
it  only  required  a  single  injection  of  Ehrlich- 
Hata  ''  606 "  to  render  anyone  exempt 
from   syphilis   for    all    time.     This    belief, 

170 


THE  CHEMOTHERAPY  OF  SYPHILIS 

which  to-day  is  still  almost  general,  is 
the  reason  why  most  syphilitic  patients  who 
have  been  treated  with  "  606 ''  have  not 
watched  themselves,  and  their  bodies  respec- 
tively, with  the  greatest  care  for  the  appear- 
ance of  any  suspicious  symptoms.  Neither 
have  they  reported  themselves  to  the 
medical  man  at  regular  intervals,  as  is 
always  required  to  be  done  with  mercurial 
therapy,  even  when  there  is  apparently 
a  complete  absence  of  symptoms.  This 
may  have  contributed  to  the  reason  why 
Wechselmann  and  many  other  teachers 
have  seen  so  few  of  their  patients  again  who 
had  been  treated  with  arsenobenzol.  There 
is  no  reason  why  all  these  patients  who 
failed  to  report  themselves  should  have 
been  cured.  Indeed,  it  is  just  the  fact 
that  the  manifest  symptoms,  under  some 
circumstances,  may  be  so  slight  that  they 
are  hardly  perceptible,  and  often  disappear 
surprisingly  rapidly,  even  without  specific 
treatment,  which  makes  this  disease  such  a 
terrible  one,  and  so  full  of  danger  for  the 

171 


THE  THERAPY  OF  SYPHILIS 

general  public.  Apparently  healthy  patients, 
who  are  suffering  from  this  disease  in  the 
latent  stage,  may  occasionally  spread  in- 
fection if  rapidly  passing  specific  symptoms 
arise,  which  are  often  slight  and  unnoticed. 
I  have  unfortunately  been  able  to  convince 
myself  of  the  possibility  of  this  in  one  of 
the  early"  cases  described  above,  which  I 
treated,  in  which  a  patient  infected  a  girl 
with  syphilis  a,bout  two  months  before  the 
outbreak  of  the  general  symptoms. 

10.  Secondary  Effects. 

In  considering  the  question  of  the  second- 
ary effects  to  which  this  new  preparation 
may  give  rise,  we  must,  like  Neisser,  dis- 
tinguish purely  local  disturbances,  which 
appear  at  the  seat  of  injection,  and  general 
secondary  effects.  As  the  former  depend 
chiefly  upon  the  manner  of  administering 
the  drug,  I  have  refrained  from  giving  them 
until  the  different  methods  of  solution  and 
forms  of  application  had  been  discussed. 

172 


THE  CHEMOTHERAPY  OF  SYPHILIS 

Most  teachers  have  expressed  themselves 
as  follows,  with  regard  to  the  general 
secondary  effects  of  the  preparation  ''  606  '' 
— namely,  that  these  are  comparatively  of 
a  very  insignificant  nature,  and  that  arseno- 
benzol,  even  in  larger  doses,  is  relatively 
innocuous  for  the  organism.  Nevertheless, 
secondary  effects  have  been  seen  on  various 
sides,  some  of  which  were  of  a  very  grave 
kind,  and  these  have  made  this  innocuous- 
ness  of  the  Ehrlich-Hata  therapy  appear  in  a 
somewhat  different  light.  It  is,  however, 
important  that  the  practitioner  should  be 
thoroughly  acquainted  with  all  these  obser- 
vations, and  therefore  they  are  given  in 
detail  here. 

Fever  is  a  regular  symptom  which  appears 
after  the  administration  of  ''  606/'  In  the 
majority  of  cases  with  intravenous  injec- 
tion it  sets  in  with  rigor  a  few  hours  after 
the  injection,  and  runs  up  to  39*5°  to  40° 
centigrade,  but  often  falls  within  a  few  hours 
(Schreiber,  A.  Neisser,  Geronne  and  Hug- 
genberg,  and  Iversen) .   In  intramuscular  and 

173 


THE  THERAPY  OF  SYPHILIS 

subcutaneous  injections  the  fever  generally 
begins  one  or  even  two  days  later,  is  not 
so  high,  and  as  a  rule  finally  drops  again. 
Schlesinger,  however,  observed  high  fever  in 
one  case  for  three  weeks  ;  there  was  no  local 
infection  present.  Neisser's  observations 
show  that  no  fever  arises  after  the  injection 
of  non-syphilitic  patients.  He  therefore 
regards  fever  after  an  arsenobenzol  injection 
as  a  general  reactionary  phenomenon,  and 
attributes  it  to  the  toxic  action  of  the 
endotoxines  liberated  by  the  destruction  of 
spirochaetes.  Very  often  phenomena  of 
drug  exanthemata  accompany  the  appear- 
ance of  fever.  Thus,  Wechselmann  observed 
a  morbillous  exanthem  with  conjunctivitis. 
Spiethoff  and  Saalfeld  also,  twenty-four 
hours  after  the  infection,  saw  an  exudative 
confluent  erythema  of  the  extensor  sides  of 
the  leg  and  thigh,  with  pain  in  the  joints, 
which  reminded  one  vividly  of  exanthem 
exsudativum  multiforme.  Twenty  -  four 
hours  later  it  had  ceased  altogether. 
Frankel,    Rille   and    Grouven,  and  others, 

174 


THE  CHEMOTHERAPY  OF  SYPHILIS 

perceived  diffuse  exanthemata,  and  true 
erythema  respectively.  In  one  case,  six 
hours  after  the  injection,  Spatz  was  able 
to  detect  "  elevated,  irritating,  bright  red, 
nettle-rash-like  infiltrations,  varying  in  size 
from  a  crown  to  a  five-crown  piece,''  over 
the  whole  body  and  face,  which  again  dis- 
appeared twenty-eight  hours  later,  without 
leaving  a  trace  behind.  Herxheimer  also 
noticed  urticaria  in  one  case,  which  began 
on  the  hands,  and  then  gradually  extended 
over  the  whole  body.  Gliick  also  saw 
urticaria  and  exanthemata  in  some  cases. 
Treupel  once  perceived  a  slight  desquama- 
tion of  the  cutis  of  the  face.  Schreiber  saw 
slight  drug  exanthem  in  two  patients,  which 
first  appeared  after  eight  to  ten  days,  with 
rise  of  temperature,  and  then  again  dis- 
appeared rapidly.  Finger  was  able  to 
observe  toxic  erythema  in  four  cases, 
amongst  them  being  one  similar  to  scarla- 
tina, which  arose  with  high  temperature, 
and  persisted  for  over  a  week. 

Further,  it  is  not  unusual  for  the  fever  to 

175 


THE  THERAPY  OF  SYPHILIS 

be  accompanied  by  flatulence,  nausea,  retch- 
ing (Alt,  Kromayer,  Rille,  and  Spiethoff), 
and  in  some  cases  with  genuine  vomiting 
(Wechselmann,  Schreiber,  Neisser,  Iversen, 
Geronne,  Rille,  Gennerich,  and  von  Zeissl). 
In  intravenous  injections  especially,  fever, 
vomiting,  vertigo,  and  similar  symptoms, 
were  observed  almost  regularly,  but  as  a 
rule  they  passed  off  equally  quickly.  The 
fever,  however,  is  pretty  frequently  accom- 
panied by  acceleration  of  the  pulse,  tachy- 
cardia, and  increase  or  diminution  of  the 
blood-pressure  (Alt,  Spiethoff,  Schlesinger, 
etc.).  Ledermann  once  saw  pronounced 
slowing  of  the  pulse.  In  my  experience 
these  symptoms  may  persist  for  a  long 
time  ;  indeed,  up  to  fourteen  days,  while 
the  temperature  remains  perfectly  normal. 
The  severest  phenomena  of  the  circulatory 
System,  however,  were  seen  by  Hoffmann 
in  two  cases  ;  in  these  were  not  only  grave 
disturbances  in  the  heart's  activity,  but 
also  slight  diffusion  towards  the  right,  and 
a   systolic  bruit  after  treatment.     Hauck 

176 


THE  CHEMOTHERAPY  OF  SYPHILIS 

also  discovered  marked  disturbance  in  the 
heart's  activity  after  a  dose  of  0-3  gramme. 
Whether  the  Ehrhch  drug  is  really  so 
non-irritant  for  the  kidneys,  as  has  been 
asserted  on  various  sides,  is  a  question  I 
must  doubt  after  the  experience  of  Schle- 
singer,  who  observed  transitory  albuminuria 
in  about  half  the  cases,  or  cylinduria 
without  albumin.  Bering  also  saw  four 
cases  of  transitory  albuminuria.  Geronne 
records  slight  albuminuria  in  some  cases, 
which,  however,  disappeared  at  the  end  of 
one  to  two  days.  The  albuminuria  was 
more  pronounced  in  one  case,  and  persisted 
four  to  five  days  ;  on  the  first  day  the 
albuminous  content  was  8  per  cent.,  but 
there  were  neither  cylinders  nor  red 
blood-corpuscles  in  the  urine.  Finger 
also  observed  a  transitory  albuminuria  in 
one  case.  Volk  and  Lipschiitz  saw  albumin 
and  cylinders  secreted  from  the  urine  eight 
days  after  one  patient  had  had  an  injection. 
According  to  Pick,  a  frequently  observed 
phenomenon    is    the    diminution    of    the 

177  M 


THE  THERAPY  OF  SYPHILIS 

quantity  of  urine,  which  in  some  cases  has 
been  reduced  from  400  to  500  c.c.  per  day, 
when  the  specific  gravity  was  not  too  high 
(1015  to  1020). 

SHght  isolated  symptoms  of  disease  of 
the  intestinal  tract  have  also  been  observed. 
Iversen  saw  transitory  diarrhoea  after  intra- 
venous injections  ;  Bering  reports  intensely 
severe  intestinal  tenesmus,  which  lasted 
one  or  two  days,  in  patients  who  had  been 
treated  with  arsenobenzol.  Pinkus  saw 
transitory  diarrhoea  in  one  syphilitic  patient, 
Schulz  in  two ;  Bettmann,  Geronne,  and 
Huggenberg  also  occasionally.  Spatz  men- 
tions that  the  painful  feeling  of  thirst,  of 
which  his  patients  complained  particularly, 
occurred  in  cases  in  which  the  temperature 
did  not  exceed  37*5°  centigrade,  and  hence 
could  not  be  caused  by  fever.  Bayet 
observed  arsenical  rheumatism^  in  many 
of  the  patients  who  had  been  treated  with 
arsenobenzol.  about  fourteen  davs  after 
the  injection. 

Distinctly    graver    symptoms    were    de- 

178 


THE  CHEMOTHERAPY  OF  SYPHILIS 

scribed  by  Bohac  and  Sabotka  in  the  three 
following  cases.     They  observed  : 

''  I.  Retention  of  urine,  the  duration  of 
which  varied,  reaching  to  half  a  day. 
In  one  case,  which  could  not  be 
estimated  at  the  time  this  work  was  con- 
cluded, it  had  certainly  extended  over  a 
period  of  more  than  nine  days  ;  after  its 
cessation  there  was  considerable  difficulty 
in  micturition  left  behind.  It  was  sur- 
prising that,  with  patients  who  had  been 
given  the  smallest  amount  of  the  prepara- 
tion, ver}^  severe  symptoms  did  not  at 
once  set  in.  In  two  cases  there  were  also 
slight  quantities  of  albumin  in  the  urine, 
without  cylinders. 

''2.  The  patellar  reflex  was  absent  m  all 
the  cases,  as  well  as  a  whole  series  of 
reflexes  which  are  usually  tested.  True, 
their  condition  conceivably  had  not  been 
examined  before  the  commencement  of  the 
treatment. 

''3.  In  two  cases  there  was  unusually 
marked  tenesmus   of  the  rectum   (in   one 

179 


THE  THERAPY  OF  SYPHILIS 

case  this  was  perhaps  favoured  by  previous 
proctitis). 

''  Further,  in  all  three  cases  intense 
constipation  was  noticeable,  which  still 
persisted  after  an  abundant  amount  of 
nourishment  was  taken.  Despite  the  fact 
that  it  was  soon  overcome  by  means  of 
a  simple  aperient,  this  should  perhaps  not 
be  confounded  with  the  usual  sluggish- 
ness of  the  bowels  of  anyone  confined  to 
bed.'' 

The     authors     attributed    the    nervous 
symptoms  to  disturbances  in  the  spinal  cord, 
the  rectal  tenesmus  to  nervous  irritation  of 
the  intestinal  tract,  and  the  retention  of 
urine  finally  to  detrusor   paralysis.      The 
authors    are    of    opinion    that    this    new 
arsenic  preparation,  as  regards  these  symp- 
toms, has  points  of  contact  with  the  secon- 
dary effects  described  as  due  to  atoxyl.     In 
contradistinction    to    this    communication 
from  Bohac  and  Sobotka,  Privy  Councillor 
Ehrlich   has   published   the   following   de- 
claration : 

i8o 


THE  CHEMOTHERAPY  OF  SYPHILIS 

'*  Frankfurt-a.-M., 

"August  I,  1910. 

''  With  regard  to  the  article  by  Bohac  and 
Sobotka,  I  may  remark  that  132  additional 
tubes  with  the  same  operative  number  as 
those  employed  in  Prague  were  sent  to 
Fauser  (Stuttgart),  Hauck  (Erlangen),  Linser 
(Tubingen),  Rille  (Leipzig),  and  Spiethoff 
(Jena).  From  all  these  places  I  have  re- 
ceived reports  to  the  effect  that  the  dis- 
turbances described  by  the  authors  were 
never  observed.  Moreover,  nothing  of  the 
kind  has  been  reported  to  me  from  else- 
where in  the  administration  of  ^  606.' 

''  On  inquiry,  Alt  (Uchtspringe)  tele- 
graphed to  me  :  '  In  more  than  200  cases 
which  were  treated  with  ''  606 "  in  the 
Institution  here,  under  the  most  exact 
control  and  careful  examination,  especially 
with  regard  to  the  nervous  s^^stem,  nothing 
similar  to  what  occurred  in  Prague  has 
been  observed.  There  has  never  been  any 
paralysis  of  the  bladder,  retention  of  urine, 
or  the  like,  nor  any  disappearance  of  the 

181 


THE  THERAPY  OF  SYPHILIS 

reflexes.  There  must,  therefore,  have  been 
some  toxic  action  which  was  brought  about, 
either  by  decomposition  of  the  preparation 
or  by  the  addition  perhaps  of  methyl-alcohol. 
I  employ  no  basic  additions,  with  the  excep- 
tion of  a  little  solution  of  caustic  soda.' 

*'  Dorr  (Vienna)  telegraphed  also  on  my 
inquiry :  *  Sixty-eight  cases,  no  paralysis 
of  bladder ;  reflexes  tested  day  before  yester- 
day by  neurologists  in  all  accessible  patients ; 
not  absent  in  a  single  one.' 

''  Similar  telegrams  were  received  from 
Finger  (Vienna)  of  forty  cases,  Neisser  (Bres- 
lau)  of  no,  Michaelis  (Berlin)  of  sixty-eight. 

''  It  is  evident  from  the  above  that  the 
disturbances  observed  by  the  authors  were 
connected  neither  with  the  preparation 
'  606  '  itself  nor  with  any  decomposition  of 
the  special  operative  numbers.  There  must, 
therefore,  have  been  sources  of  error  in 
the  preparation  of  the  solution  or  in  the 
application.  According  to  telegraphic  news 
received  from  Sellei  (Budapest),  '  Kreibich's 
failures   are  typical  symptoms  of  methyl- 

182 


THE  CHEMOTHERAPY  OF  SYPHILIS 

alcoholic  intoxication/  This  also  agrees 
with  Alt's  telegram  and  earlier  communica- 
tions from  Aulic  Councillor  Emil  von  Gross 
(Budapest)  ;  they  must  have  been  due  to  an 
injurious  effect  of  methyl-alcohol,  which  was 
perhaps  not  quite  pure. 

''  In  conclusion,  I  must  express  my  regret 
that  the  authors  did  not  consider  it  neces- 
sary to  at  once  inform  me  of  this  occurrence, 
as  then  the  sensational  disturbance  of  a 
large  circle,  which  was  caused  by  the  article, 
would  have  been  prevented. 

''  Ehrlich." 

In  a  second  report  on  the  further  course 
of  these  cases,  Bohac  and  Sobotka  state 
that  the  longest  duration  of  the  complete 
retention  of  urine  was  ten  days,  that  of 
tenesmus  a  little  more.  The  disturbances 
of  the  patellar  reflexes,  which,  together 
with  the  remaining  reflexes,  had  been  re- 
established in  the  meanwhile,  might,  in  the 
opinion  of  the  authors,  be  explained  as  the 
influence  of  pain  starting  from  the  seat  of 

183 


THE  THERAPY  OF  SYPHILIS 

injection,  in  the  sense  of  a  voluntary  or 
involuntary  inhibition.     For  the  remainder 
of  the  secondary  effects  observed,  however, 
this  circumstance  could  not  be  taken  into 
consideration.      Neither,  in  the  opinion  of 
the  authors,  could  these  unpleasant  secon- 
dary effects  be  attributed  to  a  toxic  action 
of   the    methyl-alcohol,    as    previously,    in 
many  cases  in  which  methyl-alcohol  had 
been  employed  for  the  preparation  of  the 
solution  of  arsenobenzol,  no  similar  effect 
had    been     observed.        Further,    Ehrlich 
himself  expressed  the  opinion  {Munch.  Med. 
Wochenschrift,     1910,     p.     1576)     that    no 
objection  could  be  raised  to  the  employ- 
ment   of    methyl-alcohol    in    such    small 
quantities  as  come  into  consideration  here. 
The  authors  believe  that  the  explanation  of 
this  toxic  action  is  due  to  the  fact  that  the 
preparation  in  question  had  undergone  a 
chemical  change  and  was  decomposed.    This 
view  is  shared  by  Eitner,  who  quite  recently 
was  able  to  observe  similar  symptoms  in 
one  case — retention  of  urine,  constipation, 

184 


THE  CHEMOTHERAPY  OF  SYPHILIS 

absence  of  patellar  and  other  reflexes. 
Buschke  and  his  assistant  Fischer,  however, 
regard  this  action,  like  those  they  them- 
selves observed,  and  which  are  given  below, 
as  well  as  many  reports  published  pre- 
viously, as  being  due  to  the  neurotropic 
action  of  the  arsenobenzol. 

Another  thing,  which  perhaps  speaks  in 
favour  of  the  possibility  of  a  neurotropic 
action  in  Buschke's  sense,  is  the  fact  that 
slight  relapses  occur  in  the  eyes  and  organs 
of  hearing  particularly,  and  to  this  I  have 
already  referred. 

Latterly,  Finger  has  reported  some  obser- 
vations, and  these  directly  confirm  the 
assumption  of  Buschke.  In  one  of  these 
cases,  a  patient  developed  violent  headache, 
vertigo,  and  optic  disturbances  two  months 
after  a  Hata  injection  of  0*45  gramme. 
Objective  examination  revealed  oculo- 
motoric  paresis  on  the  right  side,  paralysis 
of  the  levator  palpebrae  superioris  and  of 
the  rectus  internus,  as  well  as  commencing 
optical  neuritis  of  the  left  side.     As  it  was 

185 


THE  THERAPY  OF  SYPHILIS 

assumed  that  this  was  perhaps  due  to  a 
relapse,  the  patient  was  given  a  fresh  Hata 
injection  also  of  0*45  gramme.     Neverthe- 
less, this,  as  well  as  mercurial  and  iodine 
treatment,  remained  not  only  unsuccessful, 
but  optical  neuritis  of  the  right  side  set 
in.     With   a   second   patient,    optical   dis- 
turbances set  in  three  months  after  the 
injection,  and  were  characterised  by  abdu- 
cens  paralysis.     In  a  third  similar  case  which 
Finger    observed,   the  patient   complained 
of  optical  disturbances  three  months  after  an 
injection  of  0*45  gramme.     On  examination, 
it  was  found  that  there  was  sluggish  reaction 
of  the  pupils,  anisocoria,  bilateral  contraction 
of  the  visual  field,  retraction  of  the  temporal 
halves  of  both  pupils,  therefore,  commencing 
bilateral  optical  atrophy.     Finally,  in  the 
fourth  case,  three  months  after  the    injec- 
tion and  eight  after  infection,  optical  dis- 
turbances were  perceived,  and  right  ocular 
peripheral  chorioiditis,  with  central  vitreous 
opacity.     In  three  further  cases  *'  peculiar 
phenomena,  partly  of  a  disturbing  nature," 

136 


THE  CHEMOTHERAPY  OF  SYPHILIS 

were  found  in  the  auditory  organ/  Once 
Finger  saw  isolated  interruption  of  the 
vestibular  nerves,  although  certainly  this 
was  only  transitory.  In  another  case,  a 
patient  complained  of  vertigo  and  difficulty 
in  hearing  nine  weeks  after  the  injection 
and  three  months  after  infection.  There 
was  bilateral  labyrinthal  difficulty  of  hear- 
ing, which  subsequently  remained  un- 
changed. In  the  third  case,  the  patient, 
a  girl,  aged  eighteen,  with  specific  disease 
of  about  three  months'  standing,  had 
been  given  0*45  gramme  arsenobenzol  on 
August  5.  By  August  15,  all  syphilitic 
symptoms  had  disappeared,  and  the  patient 
was  discharged  as  cured.  On  November  7, 
she  returned  on  account  of  giddiness,  head- 
ache, and  difficulty  in  hearing  ;  she  was  free 
from  syphilis,  and  the  Wassermann  reaction 
was  negative.  Here  also  labyrinthal  diffi- 
culty of  hearing,  vertigo,  and  spontaneous 
nystagmus,  were  detected,  and  later  the 
condition  remained  stationary. 

^  Compare  the  secondary  effects  of  Arsacetin,  p.  27 

187 


THE  THERAPY  OF  SYPHILIS 

Distinct  confirmation  of  the  experience 
of  Bohac  and  Sobotka  was  obtained  in  the 
communications  of  Bonhoffer,  who,  in  the 
case  of  one  patient  with  fresh  spinal 
syphilis,  after  an  injection  of  a  neutral 
emulsion,  observed  complete  paralysis  of 
the  bladder,  and  an  augmentation  of  the 
paralytic  symptoms  in  the  legs.  With  a 
second  patient,  a  paralytic,  he  witnessed  a 
severe  epileptic  attack,  with  residuary 
bilateral  hemianopsy,  etc.  According  to 
Pollack  and  Kaur,  with  one  patient  who  had 
had  0'5  gramme,  fever  up  to  40*  i°  centi- 
grade set  in,  with  strong  acceleration  of 
the  pulse  and  retention  of  urine,  which 
persisted  for  seven  days.  Rille  also  once 
observed  an  epileptic  attack  and  repeated 
pain  in  the  knees  and  legs.  Schlesinger 
several  times  testified  to  transitory  vesical 
disturbances  in  his  patients.  Herxheimer 
had  a  case  of  retention  of  urine ;  and  even 
Wechselmann  found  that  for  a  time  one 
patient  was  incapable  of  emptying  the 
bladder.     Behring  also  once  saw  detrusor 

188 


THE  CHEMOTHERAPY  OF  SYPHILIS 

paralysis.  Chrzelitzer  discovered  arsenic 
intoxication  in  patients  with  excessive 
nervous  disturbances,  and  Wechselmann, 
Pick,  Fischer,  and  Buschke  were  able 
to  prove  the  presence  of  slight  arsenicism 
in  isolated  cases.  In  Wechselmann's  wards 
three  cases  of  paralysis  of  the  peroneus  were 
observed  after  intramuscular  application. 
In  the  opinion  of  Sieskind^  these  cases  are 
to  be  attributed  to  the  mode  of  application, 
because  the  peroneus,  from  its  superficial 
position,  suffers  external  injury  far  oftener 
than  the  tibial  fibres  of  the  sciatic  nerve. 
Now,  as  these  cases  of  paralysis  appeared 
after  a  latent  period  of  a  few  days, 
Wechselmann  regards  them  as  arsenic 
intoxication  neuritis  proceeding  from  a 
deposit.  Here  probably  we  have  to  do 
principally  with  the  effect  of  pressure  of 
the  intragluteal  injection.  According  to 
Buschke  and  Fischer,  it  is  possible  that 
they  may  be  explained  as  paralysis  of  the 
extensors,  and  thus  as  a  symptom  of  an 
existing  arsenic  intoxication.     That  under 

189 


THE  THERAPY  OF  SYPHILIS 

some  circumstances  the  internal  organs  can 
also  be  injured  is  proved  by  a  case  of 
Hoffmann's,  in  which,  after  the  injection  of 
0*3  gramme  arsenobenzol  in  acid^  solution, 
he  saw  central  embolic  pneumonia  through 
escaped  thrombus  from  the  gluteal  muscles. 
Finger  once  perceived  symptoms  of  slight 
pulmonary  embolism  after  an  injection  of  a 
paraffin  emulsion  into  the  gluteus.  Duhot 
three  times  observed  haemorrhagic  excre- 
scences. Rille  saw  dyspnoea  and  icterus 
thrice.  Pinkus  also  was  once  able  to 
testify  to  icterus  after  the  administration 
of  the  Ehrlich-Hata  preparation  *'  606,'' 
and  Behring  to  augmentation  of  exist- 
ing diabetes.  That  occasionally  pregnant 
women  do  not  tolerate  the  new  Ehrlich 
drug  as  well  as  Wechselmann  and  others 
assume,  is  shown  by  the  observations  of 
Loeb  and  Gliick,  each  of  whom  observed  an 
abortion  after  the  injection. 

^  As  is  known,  Alt,  Schreiber,  and  Hoppe  warn 
practitioners  most  emphatically  against  the  injection 
of  acid  solutions. 

.190 


THE  CHEMOTHERAPY  OF  SYPHILIS 

The  practitioner  is  naturally  particularly 
interested  in  the  communications  of  fatal 
cases  which  have  occurred  after  injections 
of  arsenobenzol,  and,  respectively,  whether 
these  could  be  connected  with  the  prepara- 
tion either  directly  or  indirectly. 

Wechselmann  himself  had  three  infants 
with  pemphigus  neonatorum,  who  were 
treated  with  ''  606,''  and  died  after  fever, 
anaemia,  and  in  one  case  opisthotonus, had  set 
in.  Herzheimer  also  reported  two  such  cases 
of  the  deaths  of  syphilitic  infants.  As  I  have 
already  stated,  Wechselmann  explains  these 
fatal  cases  as  the  effect  on  the  weak  infantile 
organism  of  the  endotoxines,  which  have 
been  liberated  by  the  destruction  of 
large  quantities  of  spirochsetes.  Schreiber 
and  Hoppe  record  two  fatal  cases  in  adults, 
which,  in  the  opinion  of  the  authors,  were 
not  connected  with  the  treatment.  Iversen 
reports  a  fatal  case  in  a  woman  who  re- 
lapsed after  a  dose  of  0-3  gramme.  Acute 
nephritis,  with  haemorrhagic  exanthem,  set 
in,  and  the  post-mortem  revealed  arterio- 

191 


THE  THERAPY  OF  SYPHILIS 

sclerosis,  myocarditis,  and  other  excessive 
changes,  which  already  existed  in  the  vitally 
important  organs.  In  a  patient  who  had 
been  ill  for  years,  with  severe  disturbances 
of  speech,  auditory  aphasia,  etc.,  on  a 
syphilitic  basis,  Frankel  and  Grouven  ex- 
perienced typical  arsenical  intoxication. 
This  occurred  a  quarter  of  an  hour  after  an 
intravenous  injection  of  0*4  gramme  arseno- 
benzol  diluted  with  15  c.c.  water,  and  the 
patient  succumbed  three  and  a  half  hours 
later.  Hoffmann  mentions  a  case  of  death 
after  0*3  gramme ''606"  in  acid  solution, 
and  Spiethoff  a  further  one  after  0*5  gramme 
in  a  badly  nourished,  anaemic  person. 
Orth  showed  preparations  from  two  cases 
of  necrosis  of  the  gluteal  muscles,  after  an 
injection  of  ''  606/'  at  the  Konigsberg 
Meeting  of  Natural  Philosophers.  In  one 
of  the  cases,  death  had  occurred  ten  days 
after  the  injection ;  in  the  other,  the  fatal 
issue  had  been  caused  by  a  pharyngo- 
laryngeal  carcinoma. 

Quite  recently  details  of  a  fatal  case  were 

192 


THE  CHEMOTHERAPY  OF  SYPHILIS 

reported  by  Ehler.  This  occurred  in 
August,  1910,  subsequent  to  an  injection 
of  50  centigrammes  "  606/'  under  increasing 
symptoms  of  intoxication  exclusively  of  the 
nervous  system  (tremor,  shivering,  attacks 
of  perspiration,  loss  of  power,  etc.).  True, 
the  patient  in  question  was  paralytic,  and 
had  already  suffered  from  two  apoplectic 
attacks.  ''  Nevertheless,  before  he  came 
under  treatment  with  '  606,'  he  could  vege- 
tate, walk,  read  the  newspapers,  and  under- 
stand various  things  in  them.''  Post-mortem 
revealed  no  other  cause  of  death  beyond 
acute  parenchymatosic  degeneration  of 
the  organs. 

With  regard  to  these  fatal  cases,  Ehrlich 
expresses  himself  as  follows  : 

''  Out  of  a  large  number  of  cases,  only 
one  fatal  one  has  been  observed  (at  Jena) 
which  concerns  a  patient,  who  would  not 
have  succumbed  to  the  disease  in  any  event. 
She  was  a  weakly  person,  with  tertiary 
syphilis  of  the  larynx,  to  whom,  for  external 
reasons,   an  injection  of  an  acid  solution 

193  N 


THE  THERAPY  OF  SYPHILIS 

was  given,  a  solution  which  has  a  par- 
ticularly strong  local  irritant  effect.  I 
believe,  therefore,  that  in  this  case  death 
was  due  to  the  effect  of  shock,  which  I  hope 
I  shall  be  able  to  avoid  in  future  with  the 
new  methods  of  administration." 

The  other  groups  of  fatal  cases,  which 
hardly  reach  a  dozen,  concern  patients  ex- 
clusively with  severe  affections  of  the 
nervous  system — such  as  tabes  with  cystitis 
and  cachexia  with  bulbar  symptoms; 
further,  patients  with  extensive  cortical 
softenings  and  similar  cases.  In  one  of  these, 
microscopic  examination  gave  the  following 
result,  which  I  repeat  word  for  word  : 

"  In  the  case  of  the  dead  patient,  micro- 
scopic examination  showed  that  at  the  seat 
of  the  exit  of  the  phrenic  nerve  from  the 
upper  cervical  spinal  cord,  the  anterior 
roots  were  embedded  in  diseased  (infil- 
trated) tissue,  and  showed  slight  degenera- 
tive changes.  It  is  quite  possible  that,  in 
consequence  of  the  reaction,  irritant  or 
swollen  conditions  (oedema  ?)  may  have  been 

194 


THE  CHEMOTHERAPY  OF  SYPHILIS 

induced  by  compression  of  the  phrenic  nerve 
which  was  already  sUghtly  diseased,  and 
resulted  in  sudden  respiratory  paralysis. 

''  Now,  granting  that  this  case  in  itself  is 
grievous,  I  believe  that  its  chief  importance 
is  that  it  shows  the  greatest  caution  is 
necessary  in  administering  '  606 '  in  syphi- 
litic diseases  of  the  upper  cervical  spinal 
cord.  Unfortunately,  as  in  our  case,  it  is 
not  always  possible  to  diagnose  these 
diseases  with  certainty.'' 

It  is  evident,  from  the  communications 
on  the  secondary  effects  of  arsenobenzol 
detailed  above,  that  a  certain  organotropic 
action  may  also  be  attached  to  this  prepara- 
tion, which  occasionally  leads  to  extremely 
unpleasant  organic  disturbances.  The  toxic 
action  of  arsenobenzol  on  the  facial  and 
auditory  nerves,  which  Finger  observed,  un- 
fortunately gives  rise  to  the  conviction  that 
arsenobenzol,  under  some  circumstances, 
may  have  a  very  injurious  toxic  effect  on 
the  nerves,  although  to  a  slighter  extent 
than  atoxyl  and  arsacetin. 

195 


THE  THERAPY  OF  SYPHILIS 

II.  Epicrisis. 

There  is  no  doubt  that  a  great  advance  in 
the  therapy  of  syphiHs  is  marked  by  the 
introduction  of  organic  arsenic  preparations 
into  specific  therapy  by  Uhlenhuth,  and 
especially  by  Ehrlich's  discovery  of  dioxy- 
diamidoarsenobenzol . 

For,  on  the  one  hand,  the  new  Ehrlich- 
Hata  preparation  ''  606  ''  —  i,e,,  arseno- 
benzol — appears,  from  evidence  before  us 
up  to  the  present,  to  be  at  least  less  toxic 
than  other  similar  arsenic  preparations, 
and,  on  the  other  hand,  with  regard  to  its 
generally  prompt  and  rapid  action  on 
manifest  syphilitic  symptoms,  to  surpass 
mercury  in  many  cases.  Even  if,  as  the 
numerous  relapses  teach  us,  in  the  doses  and 
application  up  to  the  present,  a  sterilisatio 
magna  of  the  organism  has  certainly  not 
been  obtained  in  the  way  Ehrlich  imagines, 
and  in  such  a  chronic  and  complicated 
disease  as  human  syphilis  certainly  cannot 
be   obtained    (Uhlenhuth)  ;   still   we   must 

196 


THE  CHEMOTHERAPY  OF  SYPHILIS 

acknowledge  that  arsenobenzol  forms  a 
valuable  drug  for  us  medical  men  in  the 
treatment  of  syphilis.  True,  some  time 
must  still  elapse,  and  much  experience  must 
be  collected  and  questions  explained,  before 
we  learn  to  employ  the  new  remedy  cor- 
rectly and  appropriately. 

By  means  of  summarising  the  reports 
on  the  subject  before  us,  which  have  been 
kept  as  objective  as  possible,  I  think  the 
practitioner  will  be  in  a  position  to  judge 
for  himself  when,  and  respectively  in  what 
cases,  he  may  make  use  of  the  new  Ehrlich- 
Hata  drug,  how  he  has  to  administer  it,  and 
what  result  he  may  hope  to  obtain. 

With  the  apparently  relatively  slight 
toxic  action  of  arsenobenzol,  the  prac- 
titioner will  certainly  be  able  to  employ 
this  new  preparation  in  all  stages  of  syphilis. 
He  must  use  it  in  cases  which  are  refractory 
to  mercurial  and  iodine  therapy,  or  which 
have  been  but  little  influenced  by  them. 
Fortunately,  in  nearly  all  similar  cases, 
arsenobenzol  exercises  a  particularly  good 

197 


THE  THERAPY  OF  SYPHILIS 

and  satisfactory  action.  Further,  it  has 
been  observed  in  such  cases  that,  after 
an  injection  of  arsenobenzol,  mercury  has 
again  had  a  more  favourable  effect  on  any 
residue  that  still  persists.  This  is  also  the 
case  in  forms  of  the  disease,  especially  of 
the  tertiary,  malignant,  and  ulcerous  ter- 
tiary periods  respectively,  and  of  hered- 
itary syphilis,  in  which  a  single  dose  of 
^'606''  may  often  practically  have  a  life- 
saving  effect.  In  far-advanced  para-  and 
meta-syphilitic  diseases  of  the  nervous  and 
vascular  systems,  it  is  well,  as  Ehrlich 
recommends,  to  abstain  from  the  adminis- 
tration of  arsenobenzol  in  general.  For,  in 
the  first  place,  opinions  are  in  agreement 
that  here  one  may  expect  the  least  success, 
and,  especially  in  advanced  cases,  this  drug 
may  under  some  circumstances  have  a  very 
toxic  effect. 

Further,  arsenobenzol  should  be  employed 
if  frequent  relapses  occur  a  short  time  after 
a  mercurial  cure.  If  regular  cases  of  fresh 
syphilis    of    the    primary    and    secondary 

198 


THE  CHEMOTHERAPY  OF  SYPHILIS 

periods  are  treated  with  arsenobenzol,  some- 
what from  the  standpoint  of  being  able  to 
exercise  a  preventative  or  arresting  effect 
respectively,  as   in  early  treatment,  then, 
as  is  advised  by  Hoffmann,  Neisser,  Wein- 
traub,    and   others,    it   will   be   necessary, 
under  all  circumstances,  to  follow  this  up 
with  a  few  drastic  mercurial    treatments. 
For  it  is  not  merely  the  manifest  pheno- 
mena of  syphilis  we  are   treating,  and  of 
which  respectively  we  wish  to  effect  the 
disappearance.     Even  if  these  had  healed 
up   a   short   time   after   the   beginning   of 
the  specific  cure,  we  continued   the  treat- 
ment for  a  certain  time.  Indeed,  we  repeated 
whole  cures  even  if  the  patients  were  free 
from  symptoms,  ''  as ''   (I  quote  from  the 
words  of  W.  Fischer)  ''  experience  has  taught 
us  to  regard  prolonged  mercurial  therapy 
as   a  certain   prophylaxis   against   further 
relapses  and  deleterious  secondary  diseases." 
Whether  we  may  hope  for  the  fulfilment  of 
these   expectations   with   arsenic   prepara- 
tions  also,    and   especially   with   Ehrlich's 

199 


THE  THERAPY  OF  SYPHILIS 

arsenobenzol,  remains  to  be  seen  from  the 
experience  of  many  years. 

In  considering  whether  we  should  employ 
arsenobenzol  in  the  treatment  of  primary 
and  secondary  syphilis,  we  must  further 
be  influenced  by  the  question  whether  we 
have  actually  in  the  Ehrlich-Hata  prepara- 
tion one  which  is  superior  to  mercury,  and 
is  at  the  same  time  less  toxic.  We  know  that 
certain  cases  of  the  primary  and  secondary 
periods,  such  as  large  markedly  indurated 
primary  affections,  severe  glandular  swell- 
ings, papulous  exanthemata,  and  anal  and 
genital  papules,  are  less  accessible  to  the  new 
preparation  than  to  the  usual  mercurial 
therapy.  Further,  most  of  the  failures  and 
relapses  respectively,  which  have  been  ob- 
served up  to  the  present,  have  been  especi- 
ally in  the  early  secondary  period.  With  a 
few  injections,  however,  of  one  of  the  usual 
mercurial  preparations,  we  mostly  attain 
the  same  object.  Further,  these  have 
not  such  unpleasant,  and  indeed  toxic, 
secondary  effects,  as  may  sometimes,  under 

200 


THE  CHEMOTHERAPY  OF  SYPHILIS 

some  circumstances^  follow  an  injection  of 
arsenobenzol. 

In  any  case,  patients  who  have  been 
treated  with  arsenobenzol  in  the  early 
period  of  syphilis  must  be  kept  under 
careful  supervision,  even  after  the  dis- 
appearance of  the  manifest  symptoms. 
The  present  condition  of  their  disease  must 
be  explained  to  them — i.e.,  the  possibility 
of  the  appearance  of  relapses  and  the  power 
of  transmitting  infection  in  the  latent 
period — and  above  all  they  must  be  warned 
not  to  marry  too  soon  or  incautiously,  or 
again  resume  sexual  intercourse.  I  have 
already  mentioned  in  discussing  relapses 
that,  in  consequence  of  the  extremely 
favourable  first  reports  of  the  Ehrlich-Hata 
'*  606/'  the  idea  has  penetrated  into  all  lay 
circles,  ''  Cure  of  syphilis  at  one  stroke,'' 
and  an  explanation  without  reserve  is 
imperative  in  the  interest  of  universal 
welfare. 

Now,  as  regards  the  contra-indications  to 
treatment  with  arsenobenzol,   in  the  first 

201 


THE  THERAPY  OF  SYPHILIS 

place,  advanced  diseases  of  the  nervous  and 
vascular  symptoms  belong  here.  Com- 
pletely compensated  heart  troubles,  accord- 
ing to  Grassmann,  do  not  require  to  be 
excluded  from  Ehrlich  -  Hata  treatment 
without  further  question.  Naturally,  great 
caution  is  necessary  when  other  organic 
diseases  are  already  present,  especially  of 
the  kidneys,  even  when  it  is  a  question  of 
direct  syphilitic  diseases  of  these  organs. 
As  I  have  already  mentioned,  arsenobenzol 
should  not  be  applied  without  hesitation  to 
diseases  of  the  optic  nerves,  even  if  these 
rest  on  a  syphilitic  basis,  having  regard  to 
the  nature  of  this  preparation. 

Further  questions,  such  as  whether  we 
know  the  highest  innocuous  dose  for  the 
individual  injections  properly,  whether  and 
within  what  intervals  of  time  the  injec- 
tions should  be  repeated,  and  to  what 
total  dose  we  dare  go  without  injuring  the 
organism,  are,  as  I  also  mentioned  above, 
not  yet  fully  explained  at  the  present 
time. 

202 


THE  CHEMOTHERAPY  OF  SYPHILIS 

Various  authors  repeat  the  injections  in 
the  event  of  the  action  being  unsatisfactory, 
or  in  relapses,  once  to  twice  within  shorter 
or  longer  intervals,  generally  in  somewhat 
smaller  doses  than  at  the  first  injection. 
Up    to    the    present,  no    specially    toxic 
secondary  effects  have  been  observed  with 
these  repeated  injections,  but  the  cause  of 
the    disease   has   not   always   disappeared 
altogether.     In  the  occasional  repetition  of 
the  injections,  the  practitioner  must  exer- 
cise great  caution,  and  must  always  take 
into    consideration    that    if    there    is    any 
deposit    of    arsenic    present — such    as  are 
formed  by  intramuscular  and  subcutaneous 
injections,  and  can  persist  for  a  fairly  long 
time — a    cumulative    arsenic    action    may 
easily   be    set    up.     Von    Raven   cautions 
practitioners  regarding  the  frequent  repe- 
tition of  small  doses,  especially  of  arseno- 
phenylglycin,  which  is  so  closely  related  to 
arsenobenzol,  because  this  may  bring  about 
hypersensibility,  and  have  a  toxic  effect. 
Whether,  however,  the  repeated  injection  of 

203 


THE  THERAPY  OF  SYPHILIS 

arsenobenzol,  as  of  atoxyl,  may  give  rise  to 
serious  injury,  especially  of  the  optic  nerves, 
is,  in  my  opinion,  not  yet  sufficiently  deter- 
mined to  permit  of  a  general  repetition  of 
the  Ehrlich-Hata  drug. 

At  the  conclusion  of  my  work,  I  must 
not  neglect  to  express  my  sincerest  thanks 
to  my  highly  -  esteemed  chief.  Privy 
Counsellor  Uhlenhuth,  Director  of  the  Im- 
perial Health  Bureau,  and  to  my  much- 
respected  colleague.  Dr.  Arndt,  First  Assist- 
ant of  the  Imperial  University  Polyclinique 
for  Skin  and  Venereal  Diseases,  Berlin,  for 
their  kind  assistance. 


204 


LITERATURE^ 

Alt  :  "  Tentative  Treatment  of  Paralytics  with 
Arsenophenylglycin."  Mimchener  Med.  Wochen- 
schr.,  1909,  No.  29,  p.  1457. 

"  The    Newest    EhrHch-Hata    Preparation    for 

SyphiHs."     Ibid.,  1910,  No.  11,  p.  561. 

"  On  the  Technique  of  the  Treatment  with  the 

Ehrhch-Hata    Syphilitic    Drug."     Ibid.,    1910, 
No.  34,  p.  1774. 

Berliner  Klin.   Wochenschr.,   1910,  No.   27,  p. 

1293. 

Ibid.,  1910,  No.  40,  p.  1857. 

"  The  Significance  of  the  Newest  Treatment  of 

Syphilis  for  Public  Hygiene."     Zeitschr.  f.  Medi- 
zinalbeamte,  1910,  No.  14. 

Remarks  made  during  discussion  at  the  Eighty- 
Second  Meeting  of  German  Natural  Philosophers 
at  Konigsberg.  Deulsche  Med.  Wochenschr., 
1910,  No.  41,  p.  1896. 

AssMY  :  "On  the  Technique  of  Intravenous  Hata 
Injections."     Med.  Klin.,  1910,  No.  48,  p.  1898. 

Basch  :  Budapesti  Orvosi  Ujsdg,  1910,  No.  37. 

Berliner  Med.  Gesellschaft,  Therap.  d.  Gegenw., 

1910,  No.  7. 

1  Up  to  the  beginning  of  December,  191  o. 
205 


THE  THERAPY  OF  SYPHILIS 

Bertarelli,  Pasini,  Botelli  :  Giornale  italiano 
delle  malattie  veneree  e  delta  pelle,  1910,  No.  4. 

Blaschko  :  Report  of  the  German  Society  for  the 
Combating  of  Venereal  Diseases,  i9io,viii,,No.4. 

"  Critical   Observations   on   the   Ehrlich-Hata 

Treatment."  Berliner  Klin.  Wvchenschr.,  1910, 
No.  35,  p.  1611. 

Blumenthal  :  Med.  Woche.,  1902,  No.  15. 

Med.  Klin.,  1907,  No.  12. 

AND  Jacobi,  Therapeut.  Monatshefte,  July,  1907, 

and  Deutsche  Med.  Wochenschr.,  1907,  No.  26. 

BiRiNGER :  Therapeut.  Monatshefte,  August,  1903. 

BoHAC  AND  SoBOTKA !  *'  On  Undesirable  Secondary 
Effects  after  the  Employment  of  Dioxydiamido- 
arsenobenzol  ('606'  Ehrlich-Hata").  Wiener 
Klin.  Wochenschr.,  1910,  No.  30,  p.  1102. 

"  Appendix   to    the    Communication    on 

Undesirable  Secondary  Effects  after  the  Employ- 
ment of  Dioxydiamidoarsenobenzol  ('  606 ' 
Ehrlich-Hata"),     Ibid.,  1910,  No.  31. 

*'  Remarks  on  Ehrlich's  Reply,  '  On  Vesi- 
cular Disturbances  after  the  Employment  of  the 
Preparation  "  606  "  '  in  No.  30  of  this  Journal." 
Ibid.,  1910,  No.  34,  p.  1224. 

Bornemann:  Miinchener  Med.  Wochenschr.,  1905, 
No.  22. 

Brandle  and  Clingestein  :  "Results  up  till  now  with 
EhrHch  '606.' "  Med.  Klin.,  1910,  No.  34,  p.  1332. 

Breinl  and  Todd  :  Brit.  Med.  Journ.,  1907,  i.  19. 

Bressler  :  "  The  Treatment  of  Syphilis  with  the 
Ehrlich-Hata  Drug  (Dioxydiamidoarsenobenzol)." 
First  to  Third  Editions,  Halle-am-Saale. 

206 


LITERATURE 

Breuning  :  Derm.  Zentralhl.,  x.,  No.  5. 

Citron,  H.,  and  Mulzer,  P  :  "  On  the  Preparation  of 
Ready-Made  Solutions  of  Dioxydiamidoarseno- 
benzol  (Ehrlich-Hata  '606')."  Med.  Klin., 
1910,  No.  39,  p.  1531. 

Darrier  :  La  Clinique  ophthalmologtque,  1907,  No.  3. 

Dobrovits  :  "On  the  Curative  Effect  of  EhrHch 
'  606 '  on  the  Infant  through  the  Mother." 
Wiener  Med.  Wochenschr.,  1910,  No.  38,  p.  2209. 

Ibid.,  1910,  No.  40. 

DoNAGH,  Mo  :  Lancet,  ii..  No.  10,  1910. 
Dorr  :  Wiener  Klin.  Wochenschr.,  1910,  No.  26,  p.  987. 
DuHOT  :  Annales  de  la  Poly  clinique  centrale,  Brussels^ 
1910,  Nos.  5  and  6. 

"  606."     PubHshed    by    the    Brussels  Central 

Polyclinique. 

"  Unexpected  Results  in  an  Infant  with  Heredi- 
tary SyphiHs  after  treating  the  Mother  with 
'606.'''  Mi4,nchener  Med.  Wochenschr.,  1910, 
No.  35,  p.  1825. 

Ehrlich  :  "On  the  Present  Position  of  Chemo- 
therapy.'' Berichteder  Chem.  Gesellsch.,  xlii.,  No  i. 

"  Chemotherapy      of      Infectious      Diseases." 

Zeitschr.  f.    drztl.    Fortbildung,    1909,    vol.    vi.. 
No.  23,  p.  721. 

"  Chemotherapeutical   Trypanosome   Studies." 

Berliner  Klin.  Wochenschr.,  1907,  Nos.  9-12. 

"  On  Vesicular  Disturbances  after  the  Em- 
ployment of  the  Preparation  '  606.'  Reply  to 
the  Article,"  etc.  Wiener  Klin.  Wochenschr., 
1910,  No.  31,  p.  1132. 

Med.  Klin.,  1910,  No.  34,  p.  1322. 

207 


THE  THERAPY  OF  SYPHILIS 

Ehrlich:  "Does  the  Intravenous  Injection  of  *6o6' 
present  any  Special  Dangers  ?"  Munchenev  Med. 
Wochenschr.,  1910,  No.  35,  p.  1826. 

"  Chemotherapy      of      Infectious      Diseases.'* 

Zeitschr.  f.  cirztl.  Foribildung,  vol.  vi.,  No.  23, 
p.  721. 

AND  Bertheim  :  Pharm.  Ztg.,  1907,  May  i. 

Berichte  der  Deutsch.  Chem.  Gesellschafi, 

xl.,  3293. 

AND  Rata  :  "  The  Experimental  Chemotherapy 

of  Spirilloses."  Published  by  Julius  Springer, 
Berlin,  1910.  English  Translation,  Rebman 
Limited,  1911. 

Ehrmann  :  "  Some  Remarks  on  the  Action  of  the 
New  EhrHch  Preparation  '  606.'  "  Wiener  Med. 
Klin.,  1910,  No.  38,  p.  2202. 

Eitner,  E.  :  "  Collection  of  Illustrative  Cases  of 
Ehrlich  '  606.' "  Wiener  Klin.  Wochenschr., 
1910,  No.  34,  p.  1233. 

"  Vesicular  Disturbances  and  Other  Secondary 

Effects  after  an  Injection  of  Ehrlich  '  606.'  " 
MUnchener  Med.  Wochenschr.,  1910,  No.  45,  p. 

2345. 
Emery  :    "  The   Preparation   '  606.'  "     Paris,    1910, 
No.  37. 

"The  Treatment  of  Syphilis  with  the  Ehrlich 

Preparation  '  606.'  "  Proceedings  of  the  Eighty- 
Second  Meeting  of  German  Natural  Philosophers 
and  Physicians  at  Konigsberg,  on  September  20, 
1910.    Deutsche  Med.  Wochenschr.,  1910,  No.  41. 

Fauser  :  Med.  Korrespondenzbl.  d.  WiirlL  cirztl. 
Landesvereins,  July,  1910. 

208 


LITERATURE 

Favento  :  Milnchener  Med.  Wochenschr,  1910,  No.  40, 

p.  2080. 
Finger  :  Arztl.  Reform-Ztg.,  1910,  No.  14. 
"  The  Newest   Stimulants  in   the  Domain   of 

Syphilidology."      Wiener      Klin.     Wochenschr., 

1908,  No.  I,  p.  I. 

"  The   Treatment   of   SyphiHs   with   Ehrlich's 

Arsenobenzol."     Ibid.,  1910,  No.  47,  p.  1667. 

Fischer,  W.  :  "On  the  Ehrlich  Treatment  of  Syphilis." 
Therapie  d.  Gegehwart,  September,  1910,  No.  9. 

"Contributions  to  the  Treatment  of  Syphilis  with 

Ehrlich-Hata  '  606.'  "    Med.  Klin.,  1910,  No.  45. 

AND  HOPPE  :  "  The  Behaviour  of  the  Ehrlich- 
Hata  Preparation  in  the  Human  Body."  Milnch- 
ener Med.  Wochenschr.,  1910,  No.  29,  p.  1531. 

Fleckseder  :  Wiener  Klin.  Wochenschr.,  1910,  No. 

36,  p.  1279. 
FoRBAT  :  Ibid.,  1910,  No.  40. 
Frankel  and  Grouven  :  "  Practice  with  the  Ehrlich 

Drug  '  606.'  "    Milnchener    Med.     Wochenschr., 

1910,  No.  34,  p.  1771. 
FuLD  :  Semaine  Medicale,  1910,  No.  38. 
Furth  :    "  Practice  with   Ehrlich    '  606.'  "     Wiener 

Klin.  Wochenschr.,  1910,  No.  43,  p.  1524. 
Galewsky  :  Reference,  Med.  Klin.,   1910,  No.  47, 

p.  1877. 
Gennerich  :  "On  the  Treatment  of  Syphilis  with 

Ehrlich    *  606.'  "     Berliner    Klin.    Wochenschr., 

1910,  No.  38,  p.  1785. 

"  Observations  as  to  Place  of  Application  and 

Dosage  with  Ehrhch's  Treatment."     Ihid.,  1910, 
No.  46,  p.  2o8q. 

209  o 


THE  THERAPY  OF  SYPHILIS 

Gennerich:  ''On  the  Treatment  of  Syphilis  with 
EhrHch  '  606.'  "  Berliner  Klin.  Wochenschr., 
1910,  No.  1735. 

Gerber  :  "  On  the  Effect  of  the  Ehrhch-Hata  Drug 
'  606  '  on  Spirochaetes  of  the  Mouth."  Deutsche 
Med,  Wochenschr.,  1910,  No.  46,  p.  2144. 

G:^RONNE  AND  HuGGENBERG :  Reports  from  the 
Wiesbaden  Medical  Society.  Berliner  Klin. 
Wochenschr.,  1910,  No.  28. 

Glaser:  "Ehrlich'6o6.'"   Editions  1-3,  Vienna,  1910. 

Glaubermann  :  Berliner  Klin.  Wochenschr.,  1907, 
No.  36. 

Gluck  :  "  a  Short  Account  of  109  Cases  of  Syphilis 
treated  with  '606/  "  Miinchener  Med.  Wochen- 
schr., 1910,  No.  31,  p.  1638. 

GouRWiTSCH  and  Bormann  :  "The  Ehrlich-Hata 
Preparation  '  606.'  "  Deutsche  Med.  Wochen- 
schr., 1910,  No.  38,  p.  1750. 

Grassmann  :  "  Which  Heart  Diseases  form  a  Special 
Contra-indication  to  the  Employment  of  Ehrlich- 
Hata  *  606  '  ?"  Miinchener  Med.  Wochenschr., 
1910,  No.  42,  p.  2178. 

Greven  :  Ibid.,  1910,  No.  40. 

Gr6sz  :  "  Arsenobenzol  (Ehrlich  '  606  ')  in  Syphilitic 
Diseases  of  the  Eyes."  Deutsche  Med.  Wochen- 
schr., 1910,  No.  37,  p.  1693. 

Gruter  :  "  Arsenobenzol  in  External  Diseases  of  the 
Eyes."     Ibid.,  1909,  No.  10,  p.  444. 

Hallo peau  :  Bulletin  general  de  Therapeutique, 
June  23,  1907. 

AND  BouDET :  Bulletin  de  Dermatologie  et  de 

Syphiligraphie,  1907,  No.  6. 

210 


LITERATURE 

Hallopeau:  La  CUnique,  September  6,  1907 

"On   an   Abortive   Treatment   of   Syphilis   in 

Thirty  Days."    Bulletin  de  VAcademie  de  Mede- 
cine,  Third  Series,  vol.  Ixiii.,  p.  482. 
Hamel,  H.  :  "  The  Treatment  of  Syphihde  by  Means  of 
Local  Mercurial  Injections."     Annales  de  Derm, 
et  de  Syph.,  May,  1908. 
Hecker  :  "  Estimation  of  the  Efficacy  of  Ehrhch- 
Hata  '  606.'  "    Deutsche  Med.  Wochenschr    igio 
No.  46,  p.  2143.  '  ' 

Heinrich  :    "  Some  Noteworthy  Cases  of  Arsacetin 
Treatment,  with  Historic  and  Critical  Remarks." 
Therap.  Monatsh.,  1910,  November  number 
Henius  :  Inaugural  Dissertation.     Giessen,  1902 
Hermann  :  "  Some  Remarks  on  the  Effect  of  the 
New  Ehrlich  Preparation  '  606.'  "     Wiener  Med 
Wochenschr.,  1910,  No.  ^S,  p.  2202. 
Herxheimer  :  "  Arsenobenzol  and  Syphilis."    Deut. 
Med.  Wochenschr.,  1910,  No.  33,  p.  1517. 

G.,  AND  Reinke,  F.  :  "  On  the  Influence 
of  the  EhrHch-Hata  Drug  on  the  Spirochetes 
m  Congenital  Syphilis." 

AND  ScHONNEFELD,  Med.  Klin.,  1910,  No.  36, 

p.  1400. 
Heuber  :  Therap.  Monatsch.,  1910,  No.  8. 
Heuck  :  Berliner  Klin.  Wochenschr'.,  1907,  No.  35 
Heymann:      Deutsche    Med.     Wochenschr       iqqq 
No.  50.  >     /p  \f> 

Hoche  :  Munchener  Med.  Wochenschr.   1905   No  14 
Hoffmann,  E.  :  "  Appendix  to  the  Work  of  Schaudinn 

and  E.  Hoffmann  on  Spirochceta  pallida,"  etc. 

Berliner  Klin.  Wochenschr.,  1905,  No.  23. 

211 


THE  THERAPY  OF  SYPHILIS 

Hoffmann,  E.  :  *'  Upon  the  Presence  of  Spirochsetes 
in  Ulcerous  Carcinoma."  Berliner  Klin.  Woch- 
enschr.,  1905,  No.  28,  p.  880. 

"  Further  Communications  on  the  Presence  of 

Spirochceta   pallida   in   SyphiHs."     Ibid.,    1905, 
No.  32. 

"  Spirochceta  pallida  in  a  Macaque  inoculated 

with  Blood."     lUd.,  1905,  p.  46. 

"  Further  Communications  on  the  Spirochceta 

pallida,  with  Demonstration."     Derm.  Zeitschr., 
1905. 

"  On  the  Spirochceta  pallida."  Deutsche  Med. 

Wochenschr.,  No.  43,  p.  1710. 

"  The  iEtiology  of  Syphilis,"     Julius  Springer, 

Berlin,  1906. 

"  Atlas    of    Etiological    and    Experimental 

SyphiUtic  Research."     Julius  Springer,  Berlin, 
1908. 

AND  Blumenthal  :  "  Estimate  of  Sero-diagnosis 


in  Syphilis."     Derm.  Zeitschr.,  1908,  p.  23. 

"The  .Etiology  of  Syphilis."     Published  by 

Julius  Springer,  BerUn,  1910. 

"The  Treatment    of    Syphilis   with   the  New 

Ehrlich-Hata  Arsenic  Preparation."    Med.  Klin., 
1910,  No.  33,  p.  1291. 

Hollander  :  Society  of  Internal  Medicine  (Meeting  of 

July    I,    1907).     Reference    in    Berliner    Klin, 

Wochenschr.,  1907,  No.  30,  p.  974. 
HtJGEL  AND  RuETE  :  Milnchener  Klin.  Wochenschr., 

1910,  No.  39. 
Igerheimer  :    Berliner    Klin.     Wochenschr.,     1910, 

No.  33. 

ai2 


LITERATURE 

Isaac,  B.  :  "  Results  with  the  EhrHch  Preparation 
*  606  '  (Dioxydiamidoarsenobenzol)."  Berliner 
Klin.  Wochenschr.,  1910,  No.  33,  p.  1528. 

IVERSEN  :  "  On  the  Effect  of  Ehrlich's  New  Arsenic 
Preparation  ('  606 ')  in  Relapsing  Fever." 
Mtinchener    Med.   Wochenschr.,    1910,    No.    15, 

P-  777- 

"  On  the  Treatment  of  Syphilis  with  Ehrlich's 

Preparation  '  606.'  "    Ibid.,  1910,  No.  33,  p.  1723. 
Jaraux  :  Presse  Med.  Beige,  1910,  No.  37. 
Johnston,  A.  :  "  Intravenous  Injection  of  Soamin  in 

Cerebrospinal  Meningitis."     Brit.  Med.  Jo  urn., 

1910,  vol.  i.,  p.  193. 
JuNKERMANN  :  Med.  Klin.,  1910,  No.  35. 

"  On  the  Technique  of  Treatment  with   the 

Ehrlich  Preparation '  606/  "     Ibid.,  1910,  No.  40, 

p.  1572. 
JuTOCH,  Mc  :  Lancet,  ii.,  No.  10,  1910. 
JvANYi :  Wiener  Med.  Wochenschr.;  19 10,  No.  36. 
Kalb  :   "  On  the  Action  of  Ehrlich's  Arsenobenzol 

on  Syphilis  of  Children,  with  Special  Reference 

to  Congenital  Syphilis."     Ibid.,   1910,  No.  39, 

p.  1378. 
Klemperer  :    "  On    the    Treatment    of    Pernicious 

Anaemia."     Berliner    Klin.    Wochenschr.,    1908, 

No.  52,  p.  2293. 
KowALEWSKi :  "  Neuritis  Optica  as  a  Relapse  after 

Ehrlich-Hata    ('  606 ')."     Ibid.,    1910,    No.    47, 

p.  2141. 
Kren  :  "  On  the  Treatment  of  Syphilis  with  Ehr- 
lich's   Remedy."     Wiener    Klin.    Wochenschr., 

1910,  No.  45,  p.  1596. 

213 


THE  THERAPY  OF  SYPHILIS 

Koch,  R.  :  Deutsche  Med.  Wochenschr.,  1906,  No.  51 
(Supplement). 

Ibid.,  1907,  No.  2. 

Kromayer  :    Biochimica   e    Therapia   Sperimentale, 

ii.,  No.  5. 

Berliner  Klin.  Wochenschr.,  1910,  No.  27,  p.  1294. 

"  A  Convenient,  Painless  Method  of  the  EhrHch- 

Hata  Injection."     Ihid.,  No.  37,  p.  1698. 

"  Ehrlich-Hata  '  606 '  in  Ambulant  Practice." 

Ihid.,  1910,  No.  39,  p.  1791. 

"  Theoretical  and  Practical   Considerations  of 

Ehrlich-Hata '  606.' "   lUd.,  1910,  No.  34,  p.  1585. 

Landsberger  :  Therapie  der  Gegenwart,  1907,  No.  3. 

Lange  :  "  On  the  Acquirement  of  the  Wassermann 
Reaction  in  Cases  of  Syphilis  treated  with  Ehr- 
lich's  '  606/  "  {Berliner  Klin.  Wochenschr.,  1910, 
No.  36,  p.  1656. 

Lassar  :  Ihid.,  1907,  No.  22. 

Lesser,  E.  :  "  Textbook  of  Venereal  Diseases."  Tenth 
and  Eleventh  Editions.     Published  by  Vogel. 

"Treatment  of  Syphilis  in  the  Light  of  the 

Results  of  Recent  Research."     Society  for  In- 
ternal Medicine,  Meeting  of  June  10,  1907. 

LoEB  :  "  Experience  with  Ehrlich's  Dioxydiamido- 
arsenobenzol  ('  606  ')."  Miinchener  Med.  Woch- 
enschr., 1910,  No.  30,  p.  1580. 

Malinowsky  :  Przeglad  Chorob,  1910,  No.  8. 

Maass  :  Berliner  Klin.  Wochenschr.,  1907,  No.  17. 

McDonagh:  Lancet,  ii.,  No.  10,  1910. 

Meirowsky  :  "  The  Effect  of  Ehrlich's  Drug  on  the 
Syphilitic  Process."  Med.  Klin.,  1910,  No.  42, 
p.  1653. 

314 


LITERATURE 

Meirowsky  and  Hartmann  :  "  Influencing  the 
Symptoms  of  a  Hereditarily  Syphilitic  Infant 
through  the  Serum  of  Patients  who  had  previously 
been  treated  with  EhrUch's  Arsenobenzol."  Med. 
Klin.,  1910,  No.  40,  p.  1572. 

Meltzer  :  New  York  Med.  Journ.,  Ixxxii.,  No.  8. 

Metschnikoff  and  Roux  :  Annul,  de  V Institute  Pas- 
teur, vol.  xix.,  1905. 

Mesnil  and  Nicolle  :  Ihid.,  25,  i.,  1907. 

MiCHAELis,  L.  :  Demonstration  before  the  Berlin 
Clinical  Society  on  June  22,  1910.  Reference 
in  Berliner  Klin.  Wochenschr.,  1910,  No.  28. 

"  A  Hundred  and  Ten  Cases  of  Syphilis  treated 

according  to  Ehrlich-Hata.''     Ihid.,  1910,  No.  37, 

p.  1695. 

"  The    Subcutaneous    Administration    of    the 

Ehrhch-Hata  Syphilitic  Preparation."  Ihid., 
1910,  No.  33,  p.  1531. 

MiCHELi  AND  QuARELLi '.  Corriere  Sanitaria,  1910, 
No.  30. 

MiEKLEY :  "  On  the  Effect  of  Atoxylate  of  Mercury 
on  Human  Syphilis."  Deutsche  Med.  Wochen- 
schr., 1909,  No.  41. 

MiLiAN  :  Le  proces  medical,  1910,  No.  35. 

Mondschein  :  Wiener  Med.  Wochenschr.,  1910,  No. 

36. 
Moore,    Nieren stein,    and    Todel  :    Biochemical 

Journal,  1907,  ii.,  324. 
Moses  :  Berliner  Klin.  Wochenschr.,  1907,  No.  38. 
MtJLLER  :   "On  the  Therapy  of  Primary  Syphilitic 

Affection."     Med.  Klin.,  1910,  No.  48,  p.  1899. 
MuLZER,  P.  :  "On  the  Appearance  of  Spirochsetes  in 

215 


THE  THERAPY  OF  SYPHILIS 

Syphilitic  and  Other  Infected  Tissues."    Berliner 

Klin.  Wochenscher.,  1905,  No.  36,  pp.  1144-1149. 
MuLZER,  P. :  "  Collective  Reference  on  the  finding  of 

Spirochaetes  in  Syphilis."     Arch.  /.  Derm.,  1906, 

vol.  Ixxix.,  Nos.  2  and  3. 
"  On  the  Technique  and  Practical  Value  of  the 

Wassermann  Reaction."   Zeitschr.f.  Immf.,  1910, 

vol.  v.,  Nos.  2  and  3. 
AND    MiCHAELis  :    "  Hereditary    Syphilis    and 

the    Wassermann    Reaction."      Berliner    Klin. 

Wochenschr.,  1910,  No.  30. 

See  Citron. 

See  Uhlenhuth. 


Neisser,    a.  :    "  Experimental   Syphilitic   Research 

from  its   Present   Position."      Julius   Springer, 

publisher,  Berlin. 
"  On  the  Employment  of  Arsacetin  (Ehrlich) 

in  the  Treatment  of  Syphilis."     Deutsche  Med, 

Wochenschr.,  1908,  No.  35,  p.  1500. 
"  On  the  New  Ehrlich  Drug."     Open  Letter  to 

the  Editor  of  the  Deutschen  Med.  Wochenschr  if t. 

Ibid.,  1910,  No.  26,  p.  1212. 
AND  KuzNiTZKi :  "  On  the  Significance  of  Ehr- 


lich's  Arsenobenzol  for  the  Treatment  of  Syphilis. ' ' 

Berliner   Med.    Wochenschr.,    1910,    No.    32,    p. 

1485. 
NocHT  AND  Werner  :  Deutsche  Med.   Wochenschr., 

1910,  No.  34. 
Nystrom  :     "  EhrHch-Hata    Mixture."     Bjork   and 

Borjesson,  Stockholm,  1910. 
Oppenheim  :  "  On  the  Mercury-Fast  Qualities  of  the 

Spirochaetes  of  Syphilis,  together  with  Remarks 
316 


LITERATURE 

on  the  Therapy  with  Ehrlich-Hata  '  606.' ' 
Wiener  Klin.  Wochenschr.,  1910,  No.  37,  p.  1308. 
Pasini  :  "  On  a  Simple  and  Practical  Method  of  In- 
jecting the  Ehrhch-Hata  Preparation  '  606/  " 
Miinchener  Med.  Wochenschr.,  1910,  No.  47, 
p.  2461 

Corriere  sanitario,  1910,  No.  30. 

Pick  :  Imperial  Medical  Society,  Vienna.  Reference 
Wiener  Klin.  Wochenschr.,  1910,  No.  26. 

"  Report  on  the  Results  up  to  the  Present  of 

the  Treatment  of  Syphilis  with  the  Ehrhch-Hata 
Preparation  (120  Cases)."  Ibid.,  1910,  No.  33, 
p.  1193. 

Poll  AND  and  Knaur  :  "  Report  of  Fifty  Cases  of 
Syphilis  treated  with  Ehrhch-Hata  '  606/  " 
Ihid.,  1910,  No.  43,  p.  1521. 

Pritchard,  R.:  "A  Case  presenting  the  Early  Symp- 
toms of  General  Paralysis  with  Recovery  under 
Soamin."   Brit.  Med.  Journ.,  1910,  vol.  i.,  p.  192. 

RiEHL  :  "  On  the  Treatment  of  Syphilis  with  Ehr- 
lich's  Remedy."  Wiener  Klin.  Wochenschr, y 
1910,  No.  45,  p.  1594. 

Rosenthal  :  "  On  '  606/  "  Berliner  Klin.  Wochen- 
schr., 1910,  No.  47,  p.  2137. 

RuELE  :  Miinchener  Med.  Wochenschr.,  1909,  No.  14. 

Rumpel  :  Reference  Med.  Klin.,  1910,  No.  46,  p.  1837. 

Salmon,  Comptes  Rendus  Hebdom  Soc.  Biologie, 
March  22,  1907. 

Ihid.,  April  19,  1907. 

Salomon  :  "  Treatise  on  the  Treatment  of  Syphilis 
with  Ehrhch-Hata  *  606.'  "  Med.  Klin.,  1910, 
No.  42,  p.  1652. 

217 


THE  THERAPY  OF  SYPHILIS 

ScHANZ :  "  The  Ehrlich  Preparation  '  606 '  in  Diseases 
of  the  Eyes."  Munchener  Med.  Wochenschr., 
1910,  No.  45,  p.  2344. 

ScHAUDiNN  AND  HOFFMANN,  E. :  "Current  Report  on 
the  Presence  of  Spirochaetes  in  Infected  SyphiHtic 
Tissue  and  in  Papilloma."  Arheiten  aus  dem 
Kaiserlichen  Gesundheitsamte,  April  10,  1905, 
vol,  xxii.,  No.  2,  p.  527. 

ScHAUDiNN  :  "On  the  Spirochaetic  Result  in  the 
Juices  of  the  Lymphatic  Glands  of  Syphilitics." 
Deutsche  Med.  Wochenschr.,  May  4, 1805,  No.  18, 

pp.  711-714- 

Demonstration    before    the    Berlin    Medical 

Society,  May  17,  1905.  Berliner  Klin.  Wochen- 
schr., 1905,  No.  12,  p.  694. 

Conclusion  of  the  Discussion  at  the  Meeting  of 

the  Berlin  Medical  Society  on  May  24,  1905. 
Ibid.,  1905,  No.  23,  p.  733. 

"  On  the  Spirochceta  pallida  in  Syphilis  and 

the  Difference  of  this  Form  compared  to  Other 
Kinds  of  this  Genus."  Ibid.,  May  29,  1905, 
No.  22,  p.  673. 

"  On  the  Knowledge  of  the  Spirochceta  pallida.*' 

Deutsche  Med.  Wochenschr.,  October  19,  1905, 
No.  42,  p.  1665,  and  No.  43,  p.  1728. 

"  Reply  to  Attestation  before  us  (Butschli's)." 

Ibid.,  1906,  No.  2,  p.  71. 

Discussion  Remarks,   Fifteenth   International 

Congress,  Lisbon,  April  19  to  April  26,  1906. 
Reference  Derm.  Zeitschr.,  vol.  xiii.,  No.  8,  p.  573. 

ScHiLD  :  Berliner  Klin.  Wochenschr.,  1902,  No.  13. 

Derm.  Zeitschr.,  1903,  x.,  No.  i. 

218 


LITEKATURE 

ScHREiBER,  E.  :  "  On  the  Intravenous  Injection  of 
the  Ehrhch  Drug  '  606/  "  Miinchener  Med. 
Wochenschr,  1910,  No.  39,  p.  2026. 

AND  HOPPE  :  "  On  the  Treatment  of  S3^philis 

with  the  Newest  EhrHch-Hata  Arsenic  Prepara- 
tion '  606.'  "     Ibid.,  1910,  No.  27,  p.  1430. 

ScHWABE  :  "  On  the  Effect  of  Ehrlich's  Arsenobenzol 
on  Psoriasis  and  Lichen  Ruber  Planus."  Ibid., 
1910,  No.  36,  p.  1877. 

Schwartz  and  Flemming  :  "On  the  Behaviour  of 
the  EhrHch-Hata  Preparation,  Arsenophenyl- 
glycin,  of  Iodide  of  Potassium,  and  of  SubHmate, 
to  the  Wassermann  Reaction."  Ibid.,  1910, 
No.  37,  p.  1933, 

Seligmann  and  Croner  :  Deutsche  Med.  Wochenschr,, 
June  20,  1907. 

Sellei  :  "  The  CHnical  Action  of  Ehrhch's  Diamido- 
arsenobenzol  ('  606  ')."  Miinchener  Med.  Woch- 
enschr., 1910,  No.  39,  p.  2031. 

SiESKiND  :  "  Comprehensive  Report  of  375  Cases 
treated  with  the  EhrHch-Hata  Preparation." 
Ibid.,  1910,  No.  39,  p.  2027. 

Spatz,  a.  :  "  Current  Reports  on  SyphiHtic  Cases 
treated  with  the  '  Therapia  steriHsans  magna ' 
(EhrHch-Hata  Preparation)."  Wiener  Med. 
Wochenschr.,  1910,  No.  17. 

Spiethoff  :  Miinchener  Med.  Wochenschr.,  1910,  No. 
35,  p.  1822. 

Strauss  :  "  Early  Treatment  of  the  Primary  Syphi- 
Htic Affection  with  Mercurial  AppHcations  and 
Cauterization."  Derm.  Zentralbl.,  November, 
1906. 

219 


THE  THERAPY  OF  SYPHILIS 

Taege  :  "  On  the  Successful  Treatment  of  a  Syphi- 
litic Infant  by  treating  its  Nursing  Mother  with 
'  606.'  "  Milnchener  Med.  Wochenschr.,  19 10, 
No.  33,  p.  1725. 

'*  Experiences  and  Observations  with  the  Ehr- 

lich-Hata  Preparation  '  606 '  in  the  Treatment 
of  Syphilis."     Ibid.,  1910,  No.  42,  p.  2180. 

Thalmann  :  "  Syphilis  and  its  Treatment  in  the 
Light  of  Recent  Researches/'     April,  1906. 

ToMASCZEWSKi  I  "  Report  given  before  the  Charite 
Medical  Society  on  June  2,  1910."  Berliner 
Klin.  Wochenschr.,  1910,  No.  33,  p.  1553. 

ToRDAY  :  *'  Report  on  the  Ehrlich-Hata  Treatment." 
Wiener  Klin.    Wochenschr.,    1910,    No.    39,    p. 

1381. 
Treupel  :    "  Experiences   and   Considerations   with 
the  New  Ehrlich-Hata  Drug  in  Syphilitic  and 
Meta  -  Syphilitic     Diseases."       Deutsche     Med. 
Wochenschr.,  1910,  No.  30,  p.  1393. 

"  Further  Experiences  with  Ehrlich-Hata  In- 
jections in  Syphilitic  and  Meta-Syphilitic 
Diseases."     Ibid.,  No.  36,  p.  1787. 

Truffi  :    Biochimica   e    Therapia   Sperimentale,    ii., 

No.  5. 
Uhlenhuth  :   Discourse  at  the  Colonial  Congress, 

1910. 
Gross  and  Bickel  :  Researches  as  to  the  Effect 

of  Atoxyl  on  Trypanosomes  and  Spirochaetes." 

Deutsche  Med.  Wochenschr.,  1907,  No.  4. 

Discussion  Remarks,   Berlin  Medical  Society, 

February  13,  1907.    Berliner  Klin.  Wochenschr., 
1907,  No.  12,  p.  349. 

220 


LITERATURE 

Uhlenhuth  :  Discussion  remarks,  Berlin  Army  ]\Iedical 
Society,  March  21,  1907.     Society's  Minutes. 

■  AND  Gross  :  "  Researches  as  to  the  Effect  of 

Atox}^  on  Spirillosis  of  Fowls."  Arbeit  en  aiis 
dem  Kaiserlichen  Gesundheiisamte,  vol.  xxvii., 
No.  2,  1907. 

Discussion  Remarks,  Berlin   Medical   Society, 

May  15,  1907.  Berliner  Klin.  Wochenschr.,  1907, 
No.  22. 

Hoffmann  and  Roscher  :  "  Researches  as  to 

the  Action  of  Atoxyl  on  Syphilis."  Deutsche 
Med.  Wochenschr.,  1907,  No.  22. 

Discussion  Remarks,  Society  for  Internal  Medi- 
cine, June  24,  1907.     Ibid.,  1907,  No.  30. 

Hoffmann  and  Weidanz  :  "  On  the  Preventive 

Effect  of  Atoxyl  on  Syphihs  induced  Experiment- 
ally in  Apes  and  Rabbits."     Ibid.,  1907,  No.  39. 

AND  Weidanz  :  "  Researches  as  to  the  Preven- 
tive Action  of  Atoxyl  in  comparison  to  Mercury 
in  Experimental  Syphilis  of  Rabbits."  Ibid., 
1908,  No.  20. 

— —  AND  Manteufel  :  "  Chemo therapeutical  Ex- 
periments with  Some  of  the  New  Atoxylic 
Preparations  in  Spirochaetic  Diseases,  with 
Especial  Reference  to  Experimental  Syphilis." 
Zeitschr.f.  Immf.,  1908,  vol.  i.,  No.  i. 

"  On  the  Effect  of  Atoxylate  of  Mercury  in 

Spirochaetic  Diseases,  especially  in  Experi- 
mental SyphiUs."     Med.  Klin.,  1908,  No.  43. 

AND  MuLZER  :  Demonstration  before  the  Berlin 

Medical  Society  on  December  8,  1909.  Berliner 
Klin.  Wochenschr.,  1909,  No.  51. 

221 


THE  THERAPY  OF  SYPHILIS 

Uhlenhuth  and  Mulzer  :  Demonstration  before  the 
Berlin  Medical  Society  on  January  12,  1910. 
Berliner  Klin.  Wochenschr.,  1910,  No.  4. 

"  The   Experimental   Bases   of   Chemo- 

therapeutical  Researches  with  the  New  Arsenic 
Preparations  in  Spirochaete  Diseases,  with  Special 
Reference  to  the  Treatment  of  SyphiHs." 
Deutsche  Med.  Wochenschr.,  1910,  No.  27. 

Discussion  Remarks  on  Wechselmann's  Discourse, 

Microscopic  Society,  May  20,  1910.  Reference 
in  ZentralhL  /.  Bakter.,  Supplement  to  Part  I., 
vol.  xlvii. 

Discussion    Remarks    on    the   Treatment    of 

Syphilis  with  the  Ehrlich  Preparation  '  606.' 
Natural  Philosophers,  Konigsberg,  September  21, 
1910.     Deutsche  Med.  Wochenschr.,  1910,  No.  41. 

Discussion  Remarks  on  Roscher's  Discourse  to 

the  BerHn  Army  Medical  Society  at  the  Meeting 

of  November  21,  1910. 

Inquiry  into  the  Effect  of  Ehrlich's  Arsenobenzol 


in  Syphilis.     Berliner  Med.  Klin.,  1910,  Nos.  36, 

37>  38,  39.  41.  43,  46. 

VoLK  :  Wiener  Med.  Wochenschr.,  1910,  No.  35. 

Wassermann,  a.,  and  Bruck  :  "  Is  the  Complement 
Formation  on  the  Arise  of  Specific  Deposit  a 
Phenomenon  which  is  dependent  on  the  Pre- 
cipitation, or  the  Effect  of  Amboceptors  ?" 
Med.  Klin.,  1905,  p.  1409. 

Munchener  Med.  Wochenschr.,  1906,  No.  49. 

Neisser,  a.,  and  Bruck,  C.  :  '*  A  Sero-Diag- 

nostic   Reaction   in   Syphilis."     Deutsche   Med. 
Wochenschr.,  1906,  No.  19,  p.  755. 

222 


LITERATURE 

Wassermann,  a.,  and  Schucht  :  "  Further  Report  on 
the  Proof  of  Specific  SyphiUtic  Substance  through 
the  Anchoring  of  the  Complement."  Zeitschr.  f. 
Hygiene  und  Infektionskrankheiten,  1906,  p.  451. 

AND  Plaut  :   "On  SyphiHtic  Antibodies  and 

Cerebrospinal  Fluid  in  Paralysis."  Deutsche 
Med.  Wochenschr.,  1906,  No.  44,  p.  1768. 

"  On  the  Development  and    Present  Position 

of  the  Sero-diagnosis  in  Syphilis."  Berliner 
Klin.  Wochenschr.,  1907,  Nos.  50  and  51. 

"  The  Sero-diagnosis  of  Syphilis  and  its  Signi- 
ficance in  Medical  Practice."  Congress  for  In- 
ternal Medicine,  Vienna,  1908. 

Miinchener  Klin.  Wochenschr.,  1908,  pp.  388  and 

745. 

M.,  AND  Meier,  Gg.  :  "  On  the  CUnical  Value  of 

the  Serum  Reaction,"  Deutsche  Med.  Wochen- 
schr., 1907,  No.  32. 

Wechselmann  :  "On  the  Treatment  of  Syphilis 
with  Dioxydiamidoarsenobenzol."  Berliner  Klin. 
Wochenschr.,  1910,  No.  27,  p.  1292. 

Discourse    given    before    the    Berlin    Medical 

Society  at  the  Meeting  of  June  22,  1910. 

Derm.  Zeitschr.,  1910,  xvii..  No.  7. 

Deutsche  Med.  Wochenschr.,  1910,  No.  32,  p.  1478. 

"  On    Local   and    General    Hyperaesthesia    on 

the  Employment  of  Dioxydiamidoarsenobenzol 

(Ehrlich  *6o6')."     Berliner  Klin.  Wochenschr., 

1910,  No.  47,  p.  2133. 
AND  Lange  :  "  On  the  Technique  of  Injection 

of  Dioxydiamidoarsenobenzol."     Deutsche  Med. 

Wochenschr.,  p.  1395,  No.  30. 

223 


THE  THERAPY  OF  SYPHILIS 

Wechselmann  and  Seeligsohn  ;  "On  the  Effect  of 
DioxydiamidoarsenobenzolontheEye."  Deutsche 
Med.  Wochenschr.,  1910,  No.  47,  p.  2189. 

Weintraub  :  "  Experience  with  the  EhrUch-Hata 
.  SyphiUtic  Remedy  '  606.'  "  Med.  Klin.,  1910, 
No.  43,  p.  1683. 

Werner,  H.  :  "  The  EhrUch-Hata  Drug  '  606  '  in 
Malaria."  Deutsche  Med.  Wochenschr.,  No.  39, 
p.  1792. 

WiCHECKiEWicz  :  Przeglad  LekarsM,  1910,  No,  39. 

Von  Zeissl:  Wiener  Med.  Wochenschr.,  1903,  No.  17. 

Ihid.,  1907,  No.  24. 

Ihid.,  1907,  No.  33. 

Ihid.,  1910,  No.  32. 

Ihid.,  1910,  No.  34. 

"  Report  on  the  Treatment  of  the  First  Hundred 

Cases  with  Ehrlich  '  606.'  "     Ihid.,  1910,  No.  38, 

p.  2203. 
Zernik  :    "  Patent    Charter    for    the    Ehrhch-Hata 

Preparation  *  606.'  "   Deutsche  Med,  Wochenschr., 

1910,  No.  37,  p.  1716. 
ZiELER  :    "  Experience   with   Ehrhch-Hata   '  606.'  " 

Ihid.,  1910,  No.  44,  p.  2040. 

"  Development   and   Results   of   the   Modern 

Arsenic  Therapy  in  Syphilis."     Miinchener  Med. 
Wochenschr.,  1910,  No.  47,  p.  2461. 


224 


INDEX 


Abdominal  pain,  28 
Abducens  paralysis,  135,  186 
Abortion  after  injection,  190 
Absence    of    visual    disturb- 
ances, 124 
of  patellar  reflex,  179 
Accelerationof  pulse,  176,  188 
Accommodation,   paresis   of, 

123 
Acetic  acid,  58,  6j,  86 
glacial,  60 
solution,  63 
Acetyl  combination,  29 
Acid,  acetic.    See  Acetic  acid 
carbonic,  64 
para  -  amino  -  phenyl- 

arsenic,  12 
solutions,  69,   81,   190, 
192,  193 
warning  against  in- 
jection of,  190 
sulphanilic,  12 
Acquired  specific  disease,  155 
Action,  indurating,  90 
organotropic,  195 
parasitotropic,  40 
and  secondary  effects  of 

"606,"  so 
toxic,  182 
Acute  nephritis,  191 

syphilitic  nephritis,  126 
Adeps  lanae  anhydricum,  68 
Administration  of  atoxylate 
of  mercury,  34 


Adults,  fatal  cases  in,  191 

Advance      in      therapy      of 
syphilis,  196 

Advanced    nervous    disease, 
202 
paralysis,  131 
vascular  disease,  202 

Affections,  gangrenous,  83 
indurated  primary,  200 
of  nervous  system,  194 
primary,  2,  4,   5,  92-98, 
144,  153.154,  155,  156, 
157,  159,  169 

Affinity,  neurotropic,  165 

Air  bubbles,  72 

Albumin,  177,  179 

Albuminuria,  35,  177 

Alcohol,  ethyl,  59 

methyl,  54.  S  6,  57 

Alkali,  62 

Alkaline  reaction,  59 

solutions,  51,  S3,  S4.  67, 
81.  155 

Alt's  method,  52,  S3 

Alypin,  85 

Amaurosis,  124,  125 

Amyloid,  chronic,  126 

Anaemia,  191,  192 

Anaesthetic,  85 

Anal  papules,  90,    103,    159, 
200 

Anamnesis,  9 

Angina,  99 

specific,  90,  98,  I  S3 


225 


THE  THERAPY  OF  SYPHILIS 


Angina  syphilitica,  22 
Animal  experiments,  4,  7,  34, 

106 
Animals,  observations  on,  48, 

49,  68 
Aniscoria,  186 
Annular  syphilides,  22 
Antitoxines,  136 
Anti-syphilitic       action      of 
atoxyl,  49 
treatment,  8 
Anus,  115,  157 
Apes,  syphilis  of,  4,  20,  47 

inoculation  of,  48 
Aphasia,  auditory,  192 
Apoplectic  attacks,  193 
Application,     intramuscular, 
81 
subcutaneous,  81,  83 
Arsacetin,  27-29,  40,  195 
and  blindness,  29 
and  deafness,  29 
description  of,  27 
toxic  action  of,  on  optic 
nerve,  28 
Arsenic,  138 
Arsenic  acid  anilin,  12 

action,  cumulative,  203 
deposit,  203 
Arsenic-fast  residue,  39 
Arsenic  intoxication,  192 
neuritis,  189 
preparations,  33,  ly,  122, 

199 
residue,    quinquevalent, 
40 
trivalent,  40 
secretion  of,  87 
Arsenical    preparations,     in- 
jections of,  6 
rheumatism,  178 
Arsenicism,  189 
Arsenobenzol,    48,    6^,    105, 
106,    108,    109,    no,    113, 
116,    117,    118,    119,    120, 
122,    123,    125,    126,    127, 


Arsenobenzol — continued : 

128,  129,  130,  131, 
132,  133,  134,  135, 
136,  144,  146,  149, 
150,  156,  157,  158, 
160,  161,  162,  164, 
165,  168,  170,  171, 
173,  174,  178,  184, 
185,  187,  190,  195, 
196,  199,  200,  201, 
202,    203,    204 

arresting  effect  of,  199 

best  effects  of,  121,  122 

effect  on  organism,   86- 
89 

expectations  of,  91 

first  report  of,  89 

neurotropic     action     of, 
185 

prophylactic  power  of,  48 

therapeutic  action  of,  91, 
92 

toxic  effect  of,  195 

value  of,  197 

when  and   how  to   use, 
197 
Arsenophenylglycin,     40-44, 
46,  128,  203 

chemical  constitution  of, 

41 

Arterio-sclerosis,  191,  192 

Arteritis  obliterans,  118 

Assimilation,  86 

Association  of  Internal  Medi- 
cine, 30 

Atonic  ulcers,  160 

Atoxyl,  6,   12-26,  ij,  39,  40, 
48,  49,   89,    112,    122, 
125,  180,  195,  204 
anti-syphilitic  action  of, 

49 
constitution  of ,  12,  13 
effect  of,  21-26 
in  human  syphilis,  2 1 
and  mercury  in  syphilis, 

30 


226 


INDEX 


Atoxyl,  secondary  effects  of, 
49.  125 
spirillicide,  action  of,  49 
in    spirillosis    of    fowls, 

18 
and  sublimate,  continued 

application  of,  29 
toxic  doses  of,  23 
toxicity  of,  26 
in  trypanosome  diseases, 
30 
Atoxylate  of  mercury,  29-37, 
48,  89 
administration     of, 

34 
and  rats,  3 1 
secondary  effects  of, 

34.  35 
Atoxylic  blindness,  phases  of, 

25 
resistance,  2$ 
Atrophy  of  optic  nerve,   28, 

39.  124 
optical,  186 
of  papilla  of  optic  nerve, 

25 

of  visual  nerves,  24 
Attacks,  apoplectic,  193 
epileptic,  42,  188 
gastric,  130 
of  perspiration,  193 
Attenuated  solutions   (intra- 
venous injection),  56 
Auditory  aphasia,  192 
nerves,  29,  195 
organ,  187 
Augmentation    of    diabetes,  j 

190 
Author  and  Citron,   method 
of,  6s,  64 

Bandages,  86 
Beads,  glass,  53 
Beard,  papules  in,  160 
Behring's  serum,  99 
Benzine  iodine,  72 


Benzol  nucleus,  1 5 
Benzolsulph  oneparamino- 
phenylarsenate  of  sodium, 

37 
Berkef eld's  bougies,  14 
Berlin  Medical  Society,   129, 

133 
Best  effect  of  arsenobenzol, 

121,  122 
Bilateral  specific  iritis,  123 
Bladder,    paralvsis    of,     181, 

182,  188 
Blaschko,  method  of,  62,  6^ 
Blindness,  24,  39 

and  arsacetin,  29 
Blisters,     pemphigous,     136, 

138 
Blood-corpuscles,  8/ 

red,  177 
Blood-pressure,     diminished, 
176 
disturbances  of,  133 
increased,  176 
Bone  disease,  103 
Bonj'-  processes,  1 16 
Bruit,  systolic,  176 
Bubo,  maxillar5^  93 

strumous,  97 
Buccal    mucous    membrane, 

156 
Bulbar  protuberance,  135 

symptoms,  194 
Bureau,  Imperial  Health,  16, 

17,  29,  204 
Buttocks,  pain  in,  81,  82 

Cachexia,  194 

Calcium  carbonate,  64,  65 

emulsion,  155 
Calf  of  leg,  85 
Calomel,  96,  iii,  139 

salve,  1 1 
Cannula,  Strauss,  79 

Schreiber  stopcock,  79 
Carbonic  acid,  64 
Cardiac  remedy,  133 


227 


THE  THERAPY  OF  SYPHILIS 


Caries,  134 

Cartilaginous  primary  forms, 

93 
Cases  which  failed  to  report 

themselves,  171 

Catheter  tap,  Posner's,  78 

Caustic  soda,  solution  of,  50, 
51.  52,  53.  54.  55.  ^7>  182 

Cauterisation,  6 

Central   nervous  organs,   in- 
jury to,  24 
system,  diseases  of, 
132 

Cerebral  syphilis,    116,    117, 
118,  127 
headache  of,  105 

Cervical  spinal  cord,  195 

Chancre,   6,    22,   47,    92,   96, 
108 

Chancres  mixtes,  97 

CharitS  Annates,  35 

Charlottenberg  United  Chemi- 
cal Works,  30 

Chemical      constitution      of 
arsenophenylglycin,  41 

Chemical  Institute,  Virchow 
Hospital,  88 

Chemotherapeutical     experi- 
ments, 33 

Chemotherapy  of  spirilloses, 

33 
of  syphilis,  12-204 

Chorioiditis,  186 

Choroid,  exudative  processes 
of,  124 

Choryza,  134 

Chronic  amyloid,  126 

intermittent     treatment 
of  syphilis,  7 

Cicatrix,  47,  1 1 1 

Circulatory    apparatus,    dis- 
turbance of,  133 

Citron  and  Author,  method 
of,  63,  64 

Cleansing  process,  93 

Cocaine,  85 


Colonial  Congress,  29,  42 

Colonies,  18 

Combined      application      of 

atoxyl  and  sublimate,  29 
Compressed  mono-sodium,  5 1 

di-sodium,  51 
Compression,  195 
Condition   of   visual   nerves, 

125 
Condylomata,  99,  10 1,  136 
Congenital  iritis,  1 74 

specific  disease  of  cornea, 
124 

syphilis,  109,  133,  155 
Conjunctivitis,  174 
Constipation,  179,  184 
Constitution  of  atoxyl,  12,  13 
Constriction,  130 
Contraction     of     vessels     of 
retina,  25 

of  visual  field,  186 
Contra-indications,  201 
Cord,  cervical  spinal,  195 

spinal,  194 
Cornea,  disease  of,  20 

congenital    specific    dis- 
ease of,  124 
Corneal  syphilis  of    rabbits, 

31 
Cortical  softening,  194 
Cranium,  periostitic  swelling 

of.  153 
vault  of,  116 
Cubital  vein,  52 
Cumulative    arsenic    action, 

203 
Curative  effect,  momentary, 

103 
Cutaneous  eruptions,  42 

malignant  syphilis,  116 
Cutis,  170 

desquamation  of  facial, 

175 
Cylinders,  177,  179 
Cylinduria,  177 
Cystitis,  194 


228 


INDEX 


Deafness  and  arsacetin,  29 

labyrinth,  127 
Death,  43 
Deaths  of  syphilitic  infants, 

191 
Decomposition,  182,  184 
Degeneration,     parenchyma- 

tosic,  193 
Degenerative  changes,  194 
Deposit  of  arsenic,  203 
Desquamation  of  facial  cutis, 

175 
Destruction    of   spirochaetes, 

174 
Detrusor  paralysis,  180,  188, 

189 
Deutschen       Medizinischen 

Wochenschrift,  18 
Deviation  of  course  of  disease 

169 
Diabetes,    augmentation    of, 

190 
Diagnosis   and   Wassermann 
reaction,  9 
serum,  7 
Diarrhoea,  178 
Dichlorate,  65 
Dichlorhydrate,  69 
Difficulty  in  hearing,  187 
Diffusion,  176 
Di-hydrochloride  of  diamido- 

arsenobenzol,  54 
Diminished     blood-pressure, 

176 
Dioxydiamidoarsenobenzol, 
44-204 
formula,  45 
Diphtheritic  surfaces,  99 
Disappearance     of     primary 
symptoms,  93,  94,  95 
of  reflexes,  181,  182,  183, 

185 
spirochaetes,  106,  107 
Disease,    advanced    nervous, 
202 
of  cornea,  20 


Disease    of    intestinal    tract, 
176 
kidney,  202 
specific,  33,  163 
vascular,  202 
Diseased  tissue,  3,  194 
Diseases   of   central  nervous 
system,  132 
gummatous  internal,  127 
meta-syphilitic,  198 
of  mucous  membrane,  99 
optic  nerve,  202 
parasyphilitic,   132,  162, 

198 
of     pharyngeal    organs, 

117 
spirilla,  27 
trypanosome,  15,  27,  39, 

41 
Disintegration  of  medullary 

sheath,  26 
Di-sodium  compound,  51 
Distilled  water,  54 
Disturbances    of   blood-pres- 
sure, 133 
of  circulatory  apparatus, 

133 

of  heart's  action,  176,  177 

local,  81 

optical,  38,  185 

organic,  195 

of  speech,  192 

of  spinal  cord,  180 

vesical,  188 

visual,  24,  25,  28 
Dosage,  1 39-141 
Dose  of  Hectine,  37 

in    intramuscular    injec- 
tion of  fowls,  46 

in   intramuscular    injec- 
tion of  apes,  47 

in  intravenous  injection, 

47 
of  apes,  47 
of  mercury,  5 
Dosis  efficiens  tolerata,  41 


229 


THE  THERAPY  OF  SYPHILIS 


Dosis  maxima  tolevata,  46 

Dourine,  16,  29 

Drastic  mercurial  treatment, 

199 
Drug  exanthemata,  174 
Dysarthria,  130 
Dysphagia,  22 
Dysphasia,  22 
Dyspnoea,  190 

Early    stage    of    secondary 
syphilis,  98-110 
treatment  of  syphilis,  5 
Effect    of    arsenobenzol    on 
primary,      secondary, 
and  tertiary  syphilitic 
diseases,  89-139 
arresting,  199 
on  heart's  action,  69 
preventative,  199 
toxic,  203 
Effects,    secondary,    -^6,    37, 

38,  43,  172-195 
Efflorescences,   specific,    108, 

ISO 
Ehrlich  drug   and   pregnant 

women,  190 
"  Ehrlich-Hata,"   6,   44,   46, 
93,  102,  107,  108,  112, 
118,     121,     122,     123, 
129,     135,     138,     139, 
141,  153,  155,  158 
"  606  "  50 
injection,  127 
preparation,  45 
therapy,    innocuousness 

of,  173 
treatment,  147 
Ehrlich    and    intramuscular 
injection,  80 
and    intravenous    injec- 
tion, 80 
Ehrlich's  method,  5  5 
Emaciation,  42,  43,  89 
Embolic  pneumonia,  190 
Embolism,  pulmonary,  190 


Emulsion,  188 

calcium  carbonate,  155 
Kromayer's,  65,  71 
neutral,  72,  81,  82,  166, 
190 
Encapsulated  foci,  166 
Endotoxines,   135,   137,   174, 

191.  . 

Epicrisis,  196-204 

Epilepsy,  43,  132 

Epileptic  attacks,  42,  188 

Episcleritis,  123 

Errors  with  regard  to  applica- 
tion of  mercury,  i 

Eruption,  no 
of  roseola,  3 

Eruptions,  cutaneous,  42 
maculo-papulous,  90 

Erythema,  174,  175 

Eschar,  necrotic,  114 

Ethyl  alcohol,  59 

Eusemin,  85 

Examination,       microscopic, 
194 

Exanthem,  153,  155,  156,  159, 

175 
exsudativum     multi- 
forme, 174 
hsemorrhagic,  191 
maculo-pustulous,  156 
morbillous,  174 
Exanthemata,  100,  10 1,  104, 
105,  175,  200 
drug,  174 
haemorrhagic,  102 
papulous,  34,  134 
Exciter  of  syphilis,  2 
Expectations    from    arseno- 
benzol, 91 
Experimental     injection     of 
rats,    mice,    rabbits,    etc., 

15 
Experiments  on  animals,  4, 
7,  34,  45-50,  106 
chemotherapeutical,  3  3 
preliminary,  189 


230 


INDEX 


Exudative       processes       of 
choroid,  124 
of  retina,  124 
Eye  trouble,  165 

affections,        hereditary 
syphilitic,  123 
Eyes,  185 


Facial  papule,  159 
nerves,  195 

paralysis,  118,  131,  151 
Faeces,  87 
Failures,  158 
Fall  of  hair,  169 
Fatal  cases,  191,  192,  i93 
in  adults,  191 
of  pemphigus  neona- 
torum, 191 
Fever,  83,  173,  174,  i75.  i/^, 

191 
First  report  of  arsenobenzol, 

89 
Fistula,  156 
Flatulence,  176 
Florid  specific  symptoms,  147 

syphilis,  44,  89,  168 
Forms  of  application,  172 
Fowler's  solution,  14,  15 
Fowls,  spirillosis  of,    17,  46, 

48,  49,  106 
Fresh  syphilis,  198 
Fuller's  earth,  86 
Fundus  oculi,  25 

Galloping  syphilis,  35 

Gangrenous  affections,  83 

Gastric  attacks,  1 30 

General  infection,  3 
reaction,  105 
secondary  effects,  172 
treatment,  when  to  begin 

it,  5 
Genital  papules,  159,  200 

Giddiness,  28,  187 

Glacial  acetic  acid,  60 

Glands,  lymphatic,  16 


Glandular  juices,  107 

swellings,  94,  97,  200 

Glass  beads,  53 

Gluteal  muscles,  53,  83,  190 
necrosis  of,  192 
region,  60,  65,  71,  72,  82 

Gluteus,  190 

Glycol,  54,  55 

Gottingen  Medical    Society, 

Granulation,  33,  84 

Grey  oil,  37 

Gumma,  113,  118,  120 

laryngeal,  117 

of  tonsil,  114,  117 
Gummata,  37,  113,  ii4.  ^S. 
116 

infectiousness  of,  10 

of  larynx,  113 

multiple,  114 

subcutaneous,  113 
1  Gummatous  infiltrations,  22 

internal  diseases,  127 

processes,  35,  117 

syphilis,  116 

ulcer,  114 

wounds,  113 

Haemorrhagic  exanthem,  191 

excrescences,  190 
Hair,  87 

fall  of,  169 
Hard  palate,  115,  116 
Hata  injection,  186 

powder,  63 
Headache,  22,  28,   102,   103, 
130.  135.  185,  187 
of  cerebral  syphilis,  105 
Hearing,  185 

difficulty  in,  187 
improvement  in,  128 
Heart  troubles,  202, 
Heart's  activity,  disturbance 
of,  176,  177 
effect  of,  69 
Hectine,  37,  3 S 


231 


THE  THERAPY  OF  SYPHILIS 


Hectine,  dose  of,  37 
Hemianopsy,  188 
Hemiplegia,  131 
Hereditary  syphilis,  133-139 
164,  198 
failure  of  "  606  "  iri; 

135 
syphilitic  eye  affections, 
123 
Herxheimer    reaction,     104, 

105,  157 
Hg,  93,  116,  121 

salicylic  injections,  66 
Hoarseness,  99 
Hollow  needle,  52 
Hot-air  treatment,  6 

water,  59 
Human  specific  disease,  S3 
Hydrarg.  atoxyl,  35 
Hydrarg.  sal,  1 1 1 
Hydrargyrum      oxycyana- 

tum,  6 
Hydrochloride  salt,  50 
Hyperaesthesia,  43 
"Hyperideal  '606,'  "  57,  140 
Hyperleucocytosis,  86 
Hyperplasia,  99,  100 
Hypersensibility,  203 
Hypertrophic  papules,  103 

Icterus,  127,  190 

Ictus  immunisotoricus ,  166 

Idiocy,  43 

Immunity,  11,  18 

Imperial  Health  Bureau.  See 

Bureau 
Imperial     University     Poly- 

clinique      for     Skin     and 

Venereal  Diseases,  204 
Impetiginous  syphilide,  156 
Impetigo  capitis,  22,  169 
Improvement     in      hearing, 

128 
Incipient  diabetes,  127 
Increase  in  weight,  88 
Increased  blood-pressure,  176 


Indurated  primary  affections, 

200 
Indurating  action,  90 
Induration,  syphilitic,  32 
Indurations,  92,  93,  94 
Infantile  syphilis,  134 
Infected   tissues  of   primary 
and    secondary 
periods,  105 
of    experimental 
syphilis,  106 
Infection,  general,  3 
local,  174 
spread  while  disease  is 

latent,  172 
transmission  of,  201 
Infections,  6 

Infectiousness  of  gummata,  10 
Infiltrated  foci,  166 
Infiltrations,   34,  83,  84,  85, 
113,  134,  157,  166 
gummatous,  22 
nettlerash-like,  175 
Influence    of    syphilitic    re- 
search     upon      mercurial 
therapy,  i-ii 
Influencing  result  of  Wasser- 
mann  reaction  by  arseno- 
benzol,  141-149 
Inguinal  gland,  157 
Inhibition,  involuntary,  184 

voluntary,  184 
Initial  sores,  90 
Injection,  abortion  after,  190 
intragluteal,  134 
intramuscular,     55,     58, 
60,  69,  71-73,  82,  85. 
87,  141,  163,  173,  203 
intravenous,    57,    75-81, 
B>7,  88,   121,   140,   154, 
167,  173,  176,  178,  192 
pain  of,  36,  85 
repetition  of,  203,  204 
seat  of,  65,  85,  86 
subcutaneous,  60,  69,  73- 
75,  88,  166,  174,  203 


232 


INDEX 


Injection,  technique  of,  71-81 
Injections    of   arsenical   pre- 
parations, 6 
of     mercurial     prepara- 
tions, 6 
Hg  salicylic,  66 
Injury,  204 

to    central    nervous    or- 
gans, 24 
of  optic  nerve,  125 
Innocuousness     of     Ehrlich- 

Hata  therapy,  173 
Inoculation  of  apes,  48 
Intercostal  neuralgia,  130 
Internal  organs,  109 

syphilis  of,  126-128 
Interruption     of     vestibular 

nerves,  187 
Interscapular  region,  69 
Intestinal   tract,  disease   of 
178 
irritation  of,  180 
Intoxication,  arsenical,  192 
methylalcoholic,  182,  183 
phenomena  of ,  28,43,  i93 
of  sleeping  sickness, 

Togo  form,  43 
of  sleeping  sickness. 
East  Africa  form, 
43 
Intragluteal  injection,  134 

region,  189 
Intramuscular      application 
81,  82,  83 
injection.    See  Injection 
of  fowls,  dose  in,  46 
Intravenous  application,  81 
82 
injection.     See  Injection 
attenuated         solu- 
tions, 56 
Schreiber        and 
Hobbe's  method, 
58 
Schreiber's  method, 
75-78 


Intravenous      injection       of 
fowls,  47 
incorporation,  68,  69 
Inunction  cure,  138 
treatment,  159 
Involuntary  inhibition,  184 
Iodide  of  potassium,  112 
Iodine,  iii,  120 
benzine,  72 
therapy,  119,  197 
tincture  of,  72 
I  treatment,  115,  186 

Iritis,  122,  123,  165 
'  bilateral  specific,  123 

papulosa,  122 
syphilitica,  23 
Irritation  of  intestinal  tract, 
180 
of  sciatic  nerve,  85 
Iversen's    method    of    intra- 
muscular     injec- 
tion, 51 
of  intravenous  inj  ac- 
tion, 51,  52 

Jarisch  Herxheimer  reaction, 

104,  105 
Joints,  pain  in,  174 
Juices,  glandular,  107 

Keratitis      parenchymatosa, 

122,  123 
Kidney  disease,  202 
Kidneys,  ^y 

effect  of  Ehrlich  drug  on 

Knees,  pam  m,  188 
Konigsberg        Meeting        of 
Natural  Philosophers,  192 
Kromayer's paraffin  emulsion, 
65-71 
effect  of,  70,  71 


Labia,  ulceration  of,  90 
Labyrinth  deafness,  127 


^33 


THE  THERAPY  OF  SYPHILIS 


Late     stage     of     secondary 
syphilis  and  tertiary  syphi- 
lis, 110-119 
Latent  period,  201 

specific  disease,  157 
stages,  mercury  in,  7 
Laryngeal  gumma,  117 
Larynx,  115 

tertiary  syphilis  of,  193 
Lecithin,  86 

Lecture  to  Magdeburg  Medi- 
cal Society,  89 
Leg,  calf  of,  85 

ulcer  of,  120 
Legs  :  increased  paralysis  of, 

188  ;  pain  in,  188 
Lesions,  primary  syphilitic,  4 
Lesser  clinique,    20,    34,    35, 

134.  182 
Lesser's  handle,  72 
Leucocytes,  87 
Leucocytosis,  86 
Leucodevwia  colli,  10 1 
Levator  palpebrse  superioris, 

paralysis  of,  185 
Lightning  pains,  129,  132 
Lip,  155 

papule  of,  159 
primary  affection  of,  93 
Liquid  paraffin,  66 
Litmus-paper,  60 
Liver,  specific  disease  of,  127 

tumour  of,  60 
Local  disturbances,  81,  172 
infection,  174 
reaction,  105 
secondary  effects,  81 
hocus  minor  is  resistenticB,  165 
Loss  of  power,  193 
Luer  syringe,  75 
Lues  cutanea  maculosa,  134 

praecox,  121 
Lungs,  109 
Lymphadenitis,      102,      107, 

108,  109 
Lymphatic  glands,  16,  98, 156 


Maculo  -  papulous    eruptions, 
90 
exanthema,  22,  134,  156 
Magdeburg   Medical   Society 

Lecture,  89 
Magnesia  usta,  133 
Mai  de  caderas,  16 
Malignant  period,  198 

syphilis,  23,  28,  35,  154, 
158,  160,  163 
and  ulcerous  tertiary 
forms         respect- 
ively, 1 19-122 
Manifest  symptoms,  8,  171 
syphilis,  196 

mercury  in,  7 
Massage,  86 
Maxillary  bubo,  93 
Medizinische  Klinik,  135 

inquiry  of,  161 
Medullary  sheath,  disintegra- 
tion of,  26 
Mental  disease,  43 
Mercurial  paraffin  emulsion, 

65 
plaster,  6 
preparations,  33 

injections  of,  6 
therapy,    104,    119,    197, 
200 
influence   of   syphi- 
litic research 
upon,  i-ii 
treatment,  115,  147,  148, 
169,  186 
Mercurialised   animals,   milk 

from,  139 
Mercury,    28,    30,    112,    119, 
120,     145,     196,     198, 
200 
and  atoxyl,  30 
atoxylate  of.  See  Atoxy- 
late 
results  of,  34 
direct  remedy  in  latent 
stages,  6 


234 


INDEX 


Mercury,    direct    remedy    in 
manifest   sy- 
philis,  7 
in   specific  dis- 
ease, 7 
doses  of,  5 
errors    with    regard    to 

application  of,  i 
general  treatment,  when 

to  begin,  2 
salicylic  acid,  ij 
Meta-arsenic  acid  anilide,  I2 
Metamorphosis,      regressive, 

22 

Meta-  and  para-syphilitic  dis- 
eases, including  tabes  and 
paralysis,  128-133 
Meta-s\philitic  diseases,  198 
Methaemoglobin     formation, 

88 
Method,  Alt's,  52,  53 
Blaschko's,  62,  63 
of    A.    Citron    and    the 

Author,  63,  64 
Ehrlich's,  55 
Iversen's,  51 
of  Michaelis,  58 
of  Schreiber  and  Hoppe, 

56 
of  Spiethoff,  60,  61,  62 
of  Wechselmann,  54 
and  Lange,  59,  60 
Methyl  alcohol,    54,    56,    57, 
182,  183,  184 
alcoholic      intoxication, 
182,  183 
iSIice,  experimental  infection 
of,  15 
relapsing  fever  of,  19,  45 
Microscopic  examination,  194 
Milk  from  mercurialised  ani- 
mals, 139 
Momentary    curative    effect, 

103 
Mono-dichlor hydrate,  8 1 
-hydrochloride,  55 


Mono-sodium  compound,  5  i 
Morbillous  exanthem,  174 
Morphia,  85 

Mucous    membrane,    buccal, 
156 
diseases  of,  99 
plaques,  98,  99 
Multiple  gummata,  114 
MiXnchenev       Medizin  isch  e 

Wochenschrift,  184 
^Muscles,    bladder,    weakness 
of,  130 
gluteal.    See  Gluteal 
of     swallowing,     weak- 
ness of,  130 
Myocarditis,  192 
MjTcomatous  tissue,  -^■^ 

Xagana,  15 
Narcotics,  86 
Xaso-labial  folds,  156 
Natural         Philosophers, 
Konigsberg  2\Ieeting  of,  192 
Nausea,  28,  176 
Necessity     for      ophthalmo- 

logical  examination,  125 
Necrosis,  42,  ^^x  84 

of  gluteal  muscles,  192 
Necrotic  eschar,  1 14 
Needle,  hollow,  52 
Negative  phase,  148 

reaction,   145,   146,    147, 

151,  187 
result,  141,  142,  143,  144, 
167,  169 
Nephritis,  28 
acute,  191 

sypnilitic,  126 
Nerves,  auditory,  29,  195 
facial,  195 
optic,  26,  123,  165,  204 

diseases  of,  202 
phrenic,  194,  195 
Nervous  diseases,  140 
symptoms,  180 
system,  19S 


235 


THE  THERAPY  OF  SYPHILIS 


N  ettlerash-like    infiltrations, 

175 
Neuralgia,  intercostal,  130 
Neuralgic  pains,  85 
Neurasthenics,  85 
Neuritis,     arsenic     intoxica- 
tion, 189 
optical,  123,  185,  186 
specific,  165 
Neuropathic  aflfinity,  165 
Neurotropic  action  of  arseno- 

benzol,  185 
Neutral  emulsion,  58,  72,  81, 
82,  166,  188 
suspension,  59 
Novocain,  85 
Nucleus,  benzol,  15 
Nurse,  wet,  137 
Nursing  mother  and  syphilitic 

infant,  136 
Nutrient  enema,  1 1 1 
Nystagmus,  187 

Observation  period,  91,  168 

extent  of,  168 
Observations  on  animals.  See 

Animals 
Oculi  fundus,  25 
Oculomotoric  paresis,  185 
CEdema,  194 
Olive  oil,  36 
Opacity,  vitreous,  186 
Ophthalmological     examina- 
tion necessary,  125 
Opisthotonus,  191 
Opium,  86 
Optic  nerve.     See  Nerves 

atrophy    of.        See 

Atrophy 
toxic  action  of  arsa- 
cetin  on,  28 
Optical  atrophy,  186 

disturbances.     See  Dis- 
turbances 
neuritis.     See  Neuritis 
Orchitis  gummosa,  115 


Organ,  auditory,  187 
Organic  disturbances,  195 
Organism,    effect   of   arseno- 

benzol  on,  86-89 
Organotrophic,  40 

action,  195 
Organs,  pharyngeal.  99 

vital,  40 
Os  coccyx,  pain  in,  82 
Ozaena  syphilitica,  134 

Pain,  abdominal,  28 

in  buttocks,  81,  82 

of  injection,  36,  85 

in  joints,  174 

in  knees,  188 

in  legs,  188 

lightning,  129,  132 

neuralgic,  85 

in  OS  coccyx,  82 

of  pressure,  86 

at  seat  of  injection,  183, 
184 

shooting,  28 
Palate,  115 

hard,  115,  116 

soft,  115 
Pallidas,  108 
Palmar  eminences,  157 
Papilla      of      optic      nerve, 

atrophy  of,  25 
Papules,  22,  90,  loi,  107,  108, 

115.  139,  155.  156,  157 
anal.     See  Anal 
in  beard,  160 
facial,  159 

genital.     See  Genital 
hypertropic,  103 
of  lip,  159 
mucous,  159 
of  tonsil,  120 
of  vagina,  90 
Papulous  deposits,  161 
exanthemata,  34 
syphilide,    34,    134,    158, 
159 


236 


INDEX 


Para-amino  -  phenyl  -  arsenic 
acid,  12 
-arsanilic     acid     of 

sodium,  27 
-arsonate  Hg,  29 
Paraffin  emulsion,  190 

Kromayer's,  65-71 
mercurial,  65 
liquid,  66 
Paralysis,    17,  42,    128,    129, 
132 
abducens.        See    Ab- 

ducens 
advanced,  131 
of  bladder.     See  Bladder 
detrusor.     See  Detrusor 
of  extensors,  189 
facial.     See  Facial 
flabby,  118 
of  legs,  188 

of  levator  palpebree  su- 
per ioris,  185 
of  peroneus,  189 
progressive,  128,  132 
of  rectus  internus,  185 
respiratory,  195 
spinal,  129,  130 
Paralytic  patients,  143 
Paraplegia,  131 
Parasites,  18,  40,  105 
Parasitotropic,  40 

action,  41 
Parasyphilitic  diseases.     See 

Diseases 
Parenchymatosic     degenera- 
tion, 193 
Paresis    of   accommodation, 
123 
oculo-motoric,  185 
Paronychia,  loi,  136 
Parrot's  pseudo-paralysis,  134 
Patellar   reflex,    absence   of, 

179 
Patients,  paralytic,  143 
specific,  143    . 
tabetic,  143 


Pemphigoidal  syphilide,  133 
Pemphigous    blisters.        See 

Blisters 
Pemphigus  neonatorum,  133, 
134.  158 
fatal  cases  of,  191 
Penis,  chancre  on,  92 
Period,  early,  201 
latent,  201 
malignant,  198 
primary,  198,  199,  200 
secondary,  198,  199,  200 
ulcerous  tertiary,  198 
Periostitic    swelling    of    cra- 
nium, 153 
Periostitis,  114,  116 
Peroneus,  paralysis  of,  189 
Perspiration,  87 
Petri  saucers,  66 
Pharyngeal  organs,  99 

diseases  of,  117 
probes,  1 1 1 
ulcer,  120 
Pharyngo-laryngeal        carci- 
noma, 192 
Phases  of  atoxylic  blindness, 

25 
Phenolphthaleln,  58,  59,  60, 

61 
Phenomena  of  intoxication. 
See  Intoxication 
reactionary,  84,  174 
retarded  syphilitic,  114 
tubero-serpiginous,  159 
Phimoses,  95 

Phrenic  nerve.     See  Nerve 
Physiological    salt    solution, 

52,  57 
Pigment,  34,  90 
Plaques,  22,  107 

mucous,  98,  99 
Plaques  muqueuses,  161 
Plaut-Vincent's  angina,  no 
Pneumonia,  embolic,  190 
Positive  reaction,    145,    146, 

147,  148,  149,  151 


237 


THE  THERAPY  OF  SYPHILIS 


Positive   result,  8,  141,   142, 

143,  144,  167,  169 
Posner's  catheter  tap,  78 
Post-mortem,  191,  193 
Potency,  89 
Power,  loss  of,  193 
Pregnant  women  and  Ehrlich 

drug,  190 
Preliminary  experiments,  33 
Preparations,   arsenic.       See 
Arsenic 
mercurial,  33 
Preventative  effect,  199 
Primary      affection.  See 

Affections 
disappearance       of. 
See      Disappear- 
ance 
of  lip,  93 
reduction  of,  93,  94, 

95 
inoculation  of  syphilis  of 

rabbits,  5 
period,  198,  199 
and   secondary   periods, 
infected  tissue  in,  105 
stage,  5 
syphilis,  200 
syphilitic  lesions,  4 
ulcer,  150 
Processes,  bony,  116 
gummatous,  117 
ulcerous,  113 
Proctitis,  180 
Progressive    paralysis.      See 

Paralysis 
Proliferation  tissue,  93 
Prophylactic,  best,  86 

power    of   arsenobenzol, 
48 
Prophylaxis,  6,  1 1 ,  1 99 
against  relapses,  199 
secondary   diseases, 
199 
Prostitutes,  164 
Prostration,  43 


Protozoal  diseases,  atoxyl  in, 

16 
Protuberance,  bulbar,  135 
Psoriasis  palmaris,  loi 

palmarum,  22 

plantaris,  10 1 
Pulmonary  embolism,  190 

syphilis,  126 
Pulp,    spleen  -  liver  -  bone- 
marrow,  4 
Pulse,  acceleration  of.      See 
Acceleration 

slowing  of,  176 
Puncture,  seat  of,  83 
Pupils,  reaction  of,  186 

retraction  of,  186 
Pure  culture,  33 

syphilis,  162 

Quinquevalent     arsenical 
residue,  40 

Rabbits ,  corneal  syphilis  of ,  3 1 
experimental     infection 

of,  15 
syphilis  of,  20,  33,  45,  46, 
48 
primary        inocula- 
tion syphilis  of,  5 
Rats  and  atoxylate  of  mer- 
cury, 31 
experimental     infection 

of,  15 
relapsing  fever  of,  19,  45 
Reaction,  alkaline,  59 
general,  105 

Jarisch-Herxheimer,  104 
negative.     See  Negative 
phenomena,  84 
of  pupils,  186 
serum,  8 
specific,  33 

Wassermann,  5,  7,  8,  35, 
44,  79,  124,  141,  143, 
144,  145,  146,  147. 
151,  157.  164.  169,  187 


238 


INDEX 


Reactionary  phenomena,  174 
Record  syringe,  63,  75 
Rectum,   tenesmus    of,    179, 
180 
syphilis  of,  127 
Rectus  internus,  paralysis  of, 

185 
Red  blood-corpuscles,  177 
Reduction  of  primary  symp- 
toms.   See  Primary 
Reflexes,    disappearance    of. 

See  Disappearance 
Region,  gluteal.    See  Gluteal 
interscapular,  69 
intragluteal,  189 
Regressive     metamorphosis, 

22 
Relapse,  147,  203 

prophylaxis      against, 
199 
Relapses,  121,  149-172 
Relapsing  fever,  30,  31,  49 

of  mice  and  rats,  1 9, 

45 
spirilla  of,  46 
Repetition  of  injection.    See 

Injection 
Residue,  arsenic-fast,  39 
Resistance,  atoxylic,  23 
Respiratory  paralysis,  195 
Result,  negative.    See  Nega- 
tive 
of  Wassermann  re- 
action, 9,  10 
positive.    See  Positive 
Results  of  atoxylate  of  mer- 
cury, 34 
Retarded    syphilitic    pheno- 
mena, 114 
Retching,  176 
Retention  of  urine,  179,  181, 

183,  184.  188 
Retina,  contraction  of  vessels 
of,  25 
exudative  processes   of, 
124 


Retraction  of  pupils,  186 

Rhagades,  134 

Rheumatism,  arsenical,  178 

Rigor,  173 

Roseola,  22,  92,  100,  104,  153, 
157,  169 
eruption  of,  3 
urticarial,  157,  158 
urticata,  100 

Rupise  syphiliticae,  10 1 

Saddle-nose,  112 

Salicylic  acid  mercury,  2)7 

Saline  solution,  61 

Salt,  hydrochloride,  50 

Salts  of  sodium,  29 

"  Salvarsan,"  50 

Saucers,  Petri,  66 

Scarlatina,  175 

Schreiber  and  Hoppe,  method 

of,  56 
Schreiber 's  method  of  intra- 
venous  injection,    75- 

stopcock  cannula,  79 
Sciatic  nerve,  189 

irritation  of,  85 
Sciatica,  85 

Sclerosis,  94,  95,  96,  97 
Sclerotic  tissue,  32,  33 
Scrotal  tissue,  2)'!) 

ulcers,  32 
Scrotum,  syphiloma  of,  33 
Seat   of   injection.     See    In- 
jection 
pain  at,  183,  184 
of  puncture,  ^^ 
Secondary  affections,  35 

of  atoxylate  of  mer- 
cury. 35 
diseases,         prophylaxis 

against,  199 
effects.     See  Effects 
of  atoxyl,  49,  125 
local,  81 
period,  early,  200 


239 


THE  THERAPY  OF  SYPHILIS 


Secondary  period  of  syphilis, 
37,  198,  199 
phenomena,  155 
symptoms,  2 
syphilis,    154,    160,    165, 
200 
early  stage  of,   98- 

IIO 

Secretion  of  arsenic,  87 
Septicaemia,  17 
Septum,  III 
Sero-diagnostic  results,  143 

reaction,  167 
Serological  examinations,  1 1 
Serous  fluid,  84 
Serpigino-ulcerous  syphilide, 

115 
Serum,  138 

Behring's,  99 

diagnosis,  7 

reaction,  8 
Shivering,  193 
Shock,  194 
Shooting  pains,  28 
Shoulder-blade,  60 
Sickness,  sleeping,  15,  16,  24, 

42,  43 
Side  groupings,  45 
"  606,"  44,  45.  46,  49,  SO,  65. 
66,  67,  78,  94.  95,  105, 
107,  108,  113,  IIS, 
116,  121,  122,  123, 
124,  128,  129,  13s, 
137,  138,  139.  142, 
146,  149,  IS3,  ISS, 
160,  164,  165,  170, 
171,  173,  181,  190, 
193,  196,  198,  201 

(a),  60 

(b),  60 

action     and     secondary 
effects  of,  50 

"  hyperideal,"  57 

intramuscular  injection, 

SS 
solution  of,  55 


Skin,  87 

Sleeping  sickness.    See  Sick- 
ness 
Slowing  of  pulse,  176 
Soamin,  38 
Sodii  />-aminophenylarsonas, 

38 
Sodium,  salts  of,  29 
Softening,  cortical,  194 
Solution,  acetic  acid,  61 
Solutions,  acid.    See  Acid 
alkaline.    See  Alkaline 
attenuated,  56 
of    caustic    soda.      See 

Caustic  Soda 
Fowler's,  14,  15 
physiological  salt,  57 
saline,  61 
of  "606,"  55 
Sores,  initial,  90 
primary,  90 
Specific  angina.    See  Angina 
disease.     See  Disease 
acquired,  155 
of  liver,  127 
mercury  in,  7 
efflorescences,   108,   150, 

178 
gravity,  178 
meningitis,  117 
neuritis,  165 
patients,  143 
reactions,  $$ 
treatment,  2,  4,  171 

and       Wassermann 
reaction,  10 
Speech,  disturbances  of,  192 
Spiethoff's      method.        See 

Method 
Spinae  iliacae  anteriores  supe- 

riores,  72 
Spinal  cord,  194 

disturbances  of,  180 
paralysis.    See  Paralysis 
phenomena  in  tabes,  105 
syphilis,  188 


240 


INDEX 


Spirilla,  47.  153 
diseases,  27 
of  relapsing  fever,  46 
Spirillicide  action  of  atoxyl 
49 
of  "  606,"  109,  1 10 
Spirilloses,  chemotherapy  of, 

33 
Spirillosis  of  fowls.  See  Fowls 
atoxyl  in,  18 
dose  of    "  606  "  in, 
46 
Spirit,  86 

SpirochcBta  gallinayum,iy,  19 

pallida,  3,  5,  t,^,  38,  104 

Spirochastes,  6,  7,  17,  18,  19, 

32,  33.47,48,68,  105,' 


106,  122,  135,  136, 

^37,  147,  148,  156, 

157-  159,  166,  167, 
191 

destruction  of ,  174 
disappearance    of,    106, 
107 
Spirochjetic    septicaemia    of 

fowls,  3 1 
Spirochaetosis  of  fowls,  3 1 
Spleen  -liver  -  bone  -  marrow 

pulp,  4 
Stacre,  primary,  ; 
Sterile  water,  56,  57 
SUrilisatio  magna,  196 
Sterilise,  41 
Stomatitis,  35 
Strauss  cannula,  79 
Strumous  bubo,  97 
Subcutaneous  cellular  tissue, 
III 
gummata,  1 1 3 
injection.    See  Injection 
method  of,   yT,,   74, 
84 
Sulcus  CO yonarius,  156 
Sulphanilic  acid,  12 
Suppuration,  84 
Surfaces,  diphtheritic,  99 


Surra,  15,  16 
Suspension,  neutral,  59 

of    solutions    which   are 
ready  for  use,  50 
Suspicious  symptoms,  170 
Swellings,  glandular,  200 
Symptoms,  bulbar,  194 
manifest,  8 
nervous,  180 
secondary,  2,  4 
Synechia,  123 

Syphilides,     100,     10 1,     102, 
140 
annular,  22 
gummatous,  116 
papulous.    See  Papulous 
pemphigoidal,  133 
tuberculous,  22 
tuberous,  114 
Syphilidologists,  167 
Syphilitic  children,  145 

disease,     typical     forms 

of,  4 
diseases     of     the     eyes, 
treatment  with  arseno- 
benzol,  122-126 
induration,  32 
infant       and       nursing- 
mother,  136 
research,    influence     of 
upon       mercurial 
therapy,  i-ii 
triumph  of,  1 1 
sequelae,  131 
tissues,  170 
ulcers,  31 
virus,  3,  4,  8,  165 
Syphilis,  i,  19,  20 

advance  in  therapy  of, 

196 
of  apes.    See  Apes 
atoxyl  in  human,  2 1 

and  mercury  in,  30 
cerebral.    See  Cerebral 
chronic       intermittent 
treatment  of,  7 


241 


Q 


THE  THERAPY  OF  SYPHILIS 


Syphilis,  congenital.  See 
Congenital 

cutaneous  malignant, 
ii6 

early  treatment  of,  5 

exciter  of,  2 

florid.    See  Florid 

galloping,  35 

gravis,  ^6 

hereditary,  133-139,  198 

human,  33 

infantile,  134 

of  internal  organs,  126- 
128 

maligna,  36 

malignant.  See  Malig- 
nant 

manifest,  196 

primary,  200 

pulmonary,  126 

of  rabbits.  See  Rabbits 
experimentally  in- 
duced, 48 

of  rectum,  127 

secondary.  See  Second- 
ary 

spinal,  188 

tertiary,  28,  35,  37,  44, 
109,  118,  154,  160 
nasal,  113 

testicular  and   cerebral, 

115 
therapy  of,  34 
ulcerosa  praecox,  23 
visceral,  127,  139 

Syphiloma  of  scrotum,  33 

Syringe,  Liier,  75 
Record,  63 

System,  nervous,  198 
vascular,  198 

Systolic  bruit,  1 76 

Tabes,  128,  129,  132,  194 

spinal  phenomena  in,  105 
Tabetic  patients,  143 
Tabo-paralysis,  129 


Tachycardia,  176 
Technique  of  injection,  71-81 
Temperature,  high,  175 
Tenesmus,  178,  183 

of  rectum,  179,  180 
Tertiary       and       malignant 
forms,  106 
nasal  syphilis,  113 
period,  198 
syphilis.    See  Syphilis 

of  larynx,  193 
ulcerous  process,  153 
ulcers,  22,  90,  115,  116, 
118 
Testicular       and        cerebral 

syphilis,  1 15 
Therapeutic    action    of    ar- 

senobenzol,  91,  92 
Therapia    sterilisans    magna, 

41.  43 
Therapy,  iodine,  119,  197 

mercurial.        See     Mer- 
curial 

of  syphilis,  34 
Thigh,  ulceration  of,  113 
Thirst,  178 
Thrombo-phlebitis,  ulcerous, 

118 
Thrombus,  190 
Thymol  acetin,  156 
Tincture  of  iodine,  72 
Tissue,  diseased,  3,  194 

myxomatous,  33 

proliferation,  93 

sclerotic,  32,  33 

subcutaneous    cellular, 
III 
Tongue,  153 

Tonsil,  gumma  of,  114,  117 
Tonsils,  99 
Toxic  action,  182 

doses  of  atoxyl,  23 

effect,  203 

of  arsenobenzol,  195 
Toxicity  of  atoxyl,  26 
Toxines,  105 


242 


INDEX 


Transmission     of     infection, 

20I 

Treatment,  anti-syphilitic,  8 
drastic  mercurial,  199 
general,  when  to  begin,  5 
hot  air,  6 
iodine,  115,  1S6 
mercurial.        See      Mer- 
curial 
specific.     See  Specific 
of  s\^hilitic  diseases  of 
the  ej-es  with  arseno- 
benzol,  122-126 
Tremor,  193 

Triumphs    of    sj-philitic    re- 
search, 1 1 
Trivalent    arsenical    residue, 

40 
Troubles,  heart,  202 
Trypanosome  diseases.     See 
Diseases 
atoxyl  and  mercury 
in,  30 
Trj^anosomes,  16,  17 
Tsetse  fly,  16 

Tubercle  of  lungs,  114,  115 
Tuberculous  syphilides,  22 
Tubero    -    serpiginous    phe- 
nomena, 159 
Tuberous  syphilides,  1 14 
Tumour  of  liver,  160 
T;^'pical   forms    of    syphilitic 
disease,  4 

Ulcer,  pharyngeal,  120 

of  leg,  120 
Ulcera  dura,  94 
Ulceration  of  thigh,  1 1 3 
Ulcerations,  22,  117,  158 

on  labia,  90 
Ulcerous,  tertiary  period,  196 

thrombo-phlebitis,     118, 
119 
Llcers,  33,  37,  m,  112,  113, 
156 

atonic,  160 


Ulcers,  scrotal,  31 
syphilitic,  31 
tertiary.    See  Tertiary 
Ulcum    durum     confunctivcs, 

123 
Ulcus  molle,  97 
United      Chemical      Works, 

Charlottenberg,  30 
Urine,  Sj,  88 

diminution  of,  177,  178 
retention    of.      See    Re- 
tention 
Urobilinuria,  87 
Urticaria.  175 
;  Urticarial  roseola,  157,  158 
i  Uvula,  112,  11^ 

I  Value  of  arsenobenzol,    197, 
i  19S 

of  mercury,  2 
;  Vascular  system,  198 
;  Vaseline  oil,  68 
I  Vault  of  cranium,  116 
Vein,  cubital,  52 
Vertigo,  176,  185,  187 
Vesical  disturbances,  188 
Vesicles,  42 

Vestibular   nerves,    interrup- 
tion of,  187 
Virchow  Hospital,   Chemical 

Institute  of,  88 
Virus,  4 

syphilitic.      See    S^'phi- 
litic 
Visceral  SA-philis,  127,  139 
Visual  disturbances,  25,  28 
absence     of,  124 
field,  contraction  of,  186 
nerves,  atrophy  of,  24 
condition  of,  125 
Vital  organs,  40 
Vitreous  opacit}^  186 
Voluntary  inhibition,  184 
Vomer,  1 1 1 
Vomiting,  28,  176 
Vulva,   115 


243 


THE  THERAPY  OF  SYPHILIS 


Warning  against  injection  of 

acid  solutions,  190 
Wassermann   reaction.      See 
Reaction 
and  diagnosis,  9 
negative    result    of, 

9,  10,  141,  142 
positive    result    of, 
5,   141,    142,    143, 

157 
and    specific    treat- 
ment, 10 
Water,  distilled,  54 


Water,  hot,  54 

sterile,  56,  57 
Weakness     of     muscles     of 
swallowing,  130 
of  bladder,  1 30 
Wechselmann's  method,  54 
and  Lange,   method  of, 
59,  60 
Weight,  increase  in,  88 
Wet  nurse,  syphilitic,  137 
When  and  how  to  use  arseno- 

benzol,  197 
Wounds,  gummatous,  113 


244 


AUTHORITIES  REFERRED  TO 


Alt,  43,45.  50,  52,  53,68,  69, 
85,  87,  89,  90,  91,  92,  127, 
129,  130,  140,  143,  176, 
183,  190 

Arndt,  204 

Aschaffenburg,  116 

Assmy.  78,  80 

Auscherlick,  124,  145 

Balzer,  21,  37 

Bardachzi,  87 

Bayet,  83,  119,  178 

Behring,  99,  131,  188,  igo 

Bergarth,  36 

Bering,    144,    154,    159,    162, 

177,  178 
Bertheim,  12,  13,  45,  46 
Bettmann,  162,  178 
Bickel,  17,  18 
Birch-Hirschfeld,  26 
Blaschko,  36,  62,  74,  104,  168 
Blumenfeld,  97,  99,  103 
Blumenthal,  11,  15 
Boas,   II 
Boethke,  36 
Bohac,  151,  179,  180,  181,  183, 

188 
Bonhoffer,  188 
Borcher,  29 
Brandenburg,  10 1 
Brandle,   87,    100,    103,    120, 

145.  152 
Breinl,  15 
Bressler,  112 


Broden,  16 

Browning,  27 

Bruck,  1 1 

Bruhns,  loi,  103, 108,  145,  164 

Buschke,  104,  165,  185,  189 

Chrzelitzer,  94,  100,  104,  117, 

163,  189 
Citron,  70,  149 
Clingestein,  87,  100,  103,  120, 

145.  152 
Cohn,  165 

I  Colle,  II 

I  Darier,  21,  23 

j  Dennecke,  96,  100,  153 

I  Dobrowicz,  137 

I  Dorr,  93,  100,  102,  120,  131, 

j       182 

I  Dreuw,  83,  164 

i  Duhot,  90,  127,  131,  137,  153, 

j       190 

1  Ehler,  193,  196,  198,  199 
I  Ehrlich,  12,  13,  16,  23,  27, 
29,  33.  34.  39,  40,  41.  43. 
44,  45,  46,  49,  50,  55.  69, 
80,  81,  91,  92,  104,  108, 
114,  116,  117,  126,  128, 
129.     137.    I39>    140,    141, 

146,  147,  148,  149,  151. 
159,  166,  167,  168,  170, 
177,  180-183,  184,  193 

Eitner,  155,  161,  184 


245 


THE  THERAPY  OF  SYPHILIS 


Fabry,  36 
Fauser,  181 
Fehr,  123 
Feldmann,  29 

Finger,  10,  11,  21,   175,  177, 
182,    185,    186,    187,    190, 

195 
Fischer,  W.,  88,  121,  152,  159, 

165,  185,  189,  199 
Frankel,  67,  94,  99,  loi,  102, 

120,    127,    134,    143,    159, 

174,  192 
Friedlander,  117,  131,  155 
Fiirb  ringer,  72 
Fiirth,  108 


Gennerich,  95,  100,  118, 
127,    142,    146,    154, 
176 

Gerber,  109 

Geronne,  94,  95,  98,  loi, 
115,  127,  131,  144,  150, 

159,  165,  173.  ^7^<  ^77' 
Gesser,  116 
Glaubermann,  19 
Gliick,  97,  99,  106,  113, 

131,  144,  152,  159,  175, 
Grassmann,  202 
Gross,  Emil  von,  18,  183 
Grosz,  123 
Grouven,  6y,  94,  99,  loi, 

108,    119,    120,    127, 

134,    139,    143.    155. 

162,  174,  192 

Halberstadter,  96,   103, 

145.  163 
Hallopeau,  21,  38 
Hammer,  29 
Hartung,  159 
Hata,  33,  45,  46,  47.  49, 

106,  185,  186 
Hauck,  21,  170,  181 
Hecker,  108 
Heinrich,  29 
Hermann,  145 


121, 
163, 


102, 

153. 
178 


122, 
190 


102, 
132, 
159. 


104, 


Herxheimer,  69,  94,  104,  109, 

114,  120,  143,  154,  161, 
175,  188,  191 

Heuber,  88 

Heymann,  28 

Hoffmann,  4,  5,  6,  10,  20,  21, 

102,  103,  104,  107,  119, 
134,  151,  159,  176,  190, 
192,  199 

Hollander,  5 

Hoppe,  50,  55,  56,  68,86,88, 

142,  150,  190,  191 
Hiibener,  17,  29 
Hiiggenberg,  94,  98,  loi,  102, 

115,  150,  173,  178 

Igersheimer,  124 
Isaac,  98,  loi,  115,  145 
Iversen,  51,  69,  93,  94,   100, 
107,    113,    140,    142,    148, 
159,  173.  176,  178,  191 

Jadassohn,  95,  161 

Jakoby,  15 

Jenssen,  28 

Johnston,  39 

Joseph,  155 

Juliusberg,  93,  loi,  119,  162 

Junkermann,  67,  69,  72,  134 

Kalb,  134,  138 

Kaur,  188 

Klausner,  87 

Klemperer,  28 

Knaur,  165 

Koch,  Robert,  16 

Kopke,  16 

Koster,  26 

Kowalewski,  165 

Kraus,  21 

Kreibich,  21,  182 

Kromayei,  65,  70,  73,  84,  100, 

103,  113,  144,  152,  163. 
176 

Kusnitzki,  151 


246 


AUTHORITIES  REFERRED  TO 


Lambkin,  2)^,  39 
Landsteiner,  10,  11 
Lange,  59,  74,  87,  141 
Lassar,  21 
Ledermann,    loi,    104,    114, 

119,  131,  153,  163,  176 
Lesser,  E.,  2,  21,  35,  36 
Lesser,  F.,  126 
Lilley,  130 

Linser,  144,  154,  161,  181 
Lipschiitz,  loi,  102,  103,  104, 

147,  159,  177 

Loeb,  6y,  88,  145,  151,  190 

McDonagh,  142,  162 

Manteufel,  30 

Marchoux,  17 

Marenesco,  138 

Meirowsky,  70,  115,  121,  127, 

138 
Mesnil,  16 
Metschnikoff,  11 
Michaelis,  L.,  11,  58,  59,  60, 

69,  73,  74,  84,  95,  100,  112, 

126,    131,    133,    143,    145, 

162,  182 
Miekley,  34,  35,  93,  94,  98,  99, 

100,    loi,    118,    119,    145, 

155 
Moore,  30 
Moses,  21 
Mouneyrat,  2,7 
Mulzer,  ^t, 

Nagelschmidt,  21 

Neisser,  A.,  4,  7,  10,  11,  20, 
27,  28,  38,  47,  68,  86,  93, 
103,    104,    105,    132,    144, 

148,  150,    151,    172,    173, 
174,  176,  182,  199 

Nicolle,  16 
Nierenstein,  30 

Oppenheim,  108 
Orth,  192 


Paderstein,  28 

Passini,  67 

Pflughoft,  29 

Pick,  96,  120,  134,  142,  145, 

177,  189 
Pinkus,  94,  98,  159,  162,  178, 

190 
Plaut,  138 
Pollack,  188 
Polland,  165 
Pritchard,  39 
Profata,  1 1 

Rapiport,  21 

Raven,  von,  43,  203 

Raubitschek,  137 

Ricord,  1 1 

Rille,  96,  100,  154,  162,  174, 

176,  181,  188,  190 
Rodheim,  16 
Roscher,  19,  21 
Rouviere,  21 
Roux,  1 1 
Ruele,  29 
Rumpel,  no 

Saalfeld,  E.,  67,  loi,  104,  163, 

174 
Sabotka,  151,  179,  180,  181, 

183,  188 
Salimpeni,  17 
Salmon,  21,  27,  131,  140 
Schanz,  24,  123 
Schaudinn,  17 
Scherber,  21 
Scherschmidt,  42 
Schindler,  96 
Schlesinger,    133,     145,    174, 

176,  177,  188 
Scholtz,    106,   126,  138,   145, 

159,  163 
Schreiber,  50,  55,  56,  68,  75, 
7^,  79,  80,  89,  93,  loi,  106, 
132,  140,  142,  150,  154, 
163,  173,  175.  176,  190, 
191 


247 


THE  THERAPY  OF  SYPHILIS 


Schulz,  96,  97,  162,  178 

Seeligsohn,  123 

Sellei,  106,  182 

Sieskind,  69,   74,  83,  84,  97, 

100,    102,    103,    105,    106, 

121,  122,  189 
Solomon,  94 
Sowade,  25,  27,  28 
Spatz,  82,  94,  100,  loi,   175, 

178 
Spiethoff,  60,  61,  68,  j},,  95, 

98,  ICO,  102,  106,  113,  134, 

143,    159,     174,    176,    161, 

181 
Stern,     96,     144,     155,     158, 

159 

Taege,  135,  136,  137,  160 
Thalmann,  5 
Thomas,  W.,  15,  16 
Tomasczewski,  11,  47,  106 
Torday,  130,  140,  145 
Treupel,    87,    123,    131,    159, 

162 
Truffi,  104,  139 

Uhlenhuth,  4,  11,  14,  16,  \j . 
18,   19,  20,  21,  24,  27,  29, 


30,  32,  i^,  34,  42,  45,  48 
49,  106,  196,  204 
Ulrich,  42 

Volk,  loi,  102,  103,  104,  147, 
159.  177 

Wassermann,  145,  146,  147 
Weber,  117,  127,  142,  154 
Wechselmann,  54,  59,  69,  y-}), 
74,  85,  88,  91,  92,  93,  100, 
loi,    no,    III,    112,    115, 
123,    124,    125,    127,    130, 
133,    13s,    141,    148,    149, 
150,    152,    158,    162,    165, 
166,    168,    171,    174     176, 
1S8,  189,  190,  191 
Weidanz,  20,  21 
Weintraub,  78,  140,  199 
Welander,  95,  10 1,  164 
Woithe,  17,  29 
Wolff,  152 
Wolters,  104,  116,  127 

Zeissl,  von,  21,  93,  97,  116, 
123,  131,  133,  139,  142, 
164,  176 

Zieler,  -^j ,  119 


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